Phenoxybenzamine selectively and irreversibly inactivates dopaminergic D2 receptors on primary cultured rat lactotrophs. Lactotrophs have several different kinds of receptors, such as dopaminergic D2, somatostatin, angiotensin II and thyrotropin-releasing hormone receptors, which stimulate or inhibit prolactin release. We have studied the specificity of phenoxybenzamine on receptors in lactotrophs. Phenoxybenzamine is a beta-haloalkylamine which alkylates chemically active radicals such as hydroxy, sulfhydryl, and amino groups. This alkylation is an irreversible chemical reaction in contrast to the receptor-secretagogue complex which is present in a state of dynamic equilibrium. Primary cultured rat adenohypophyseal cells were used in this study. A dose-response relationship was examined between concentrations of phenoxybenzamine pretreatment and prolactin release using a monolayer cell culture system. The inhibitory action of dopamine (10 mumol/l) on the control group (13.0 +/- 0.1 ng/ml or 86% inhibition relative to the control) was significantly higher than on the 0.1-mumol/l phenoxybenzamine-pretreated group (39.0 +/- 0.2 ng/ml or 58% inhibition relative to the control), but the stimulatory effect of thyrotropin-releasing hormone on prolactin release was not significantly affected up to a 10-mumol/l phenoxybenzamine pretreatment as compared with the control group. We thus selected a phenoxybenzamine concentration of 0.1 mumol/l for the next series of perifusion experiments in order to examine dynamic changes in prolactin release. The basal prolactin release was decreased to almost half by phenoxybenzamine pretreatment. The inhibitory action of dopamine (0.1 mumol/l containing 0.1 mmol/l ascorbic acid) was significantly less in the phenoxybenzamine-pretreated group (68% of the basal prolactin concentration) than in the control group (31% of the basal concentration).(ABSTRACT TRUNCATED AT 250 WORDS)


High concentrations of dopamine and epinephrine protect dopaminergic D2 receptors from inactivation by phenoxybenzamine on primary cultured rat lactotrophs. The effect of a high concentration of catecholamines on phenoxybenzamine pretreatment was examined. The efficacy of the pretreatments was monitored by testing the inhibitory action of dopamine on prolactin release. Phenoxybenzamine is a beta-haloalkylamine which alkylates and irreversibly inactivates adrenergic alpha-receptors in smooth muscle. Dopaminergic D2 receptors share several common characteristics with the alpha-receptors. Primary cultured male rat pituitary cells were used. After phenoxybenzamine (0.1 mumol/l) pretreatment, the inhibitory action of dopamine on prolactin release was significantly reduced in a perifusion system. When the cells were pretreated with phenoxybenzamine in medium containing 0.1 or 1 mmol/l dopamine, the 0.1-mmol/l dopamine did not change the effect of phenoxybenzamine on inactivation of the receptors, but the 1-mmol/l dopamine eliminated the effect of phenoxybenzamine pretreatment. These observations were confirmed with a static monolayer culture system. The observations illustrate that a high concentration of dopamine forms a D2 receptor-dopamine complex and protects the D2 from inactivation by phenoxybenzamine. When the cells were pretreated with 0.1 mumol/l phenoxybenzamine in a medium containing 1 mmol/l epinephrine, the effect of the phenoxybenzamine was also eliminated, suggesting that a sufficient amount of D2 receptor-epinephrine complex was formed to protect the receptor from inactivation. The hormone release in response to a secretagogue depends on its affinity and intrinsic activity. It is, therefore, suggested that the intrinsic activity of epinephrine is much lower than that of dopamine on prolactin release, since the D2 receptor-epinephrine complex is as stable as the D2 receptor-dopamine complex, and the inhibitory action of epinephrine on prolactin release is less than 10% of that of dopamine.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of insulin on LHRH release by perifused hypothalamic fragments. Insulin-deficient states are associated with an impaired function of the hypothalamic-pituitary-gonadal axis, but the mechanisms underlying hypothalamic alterations in experimental diabetes are still unknown. We investigated the effect of glucose concentrations, in the presence and absence of insulin, on LHRH release from perifused hypothalamic fragments from female adult ovariectomized rats. Glucose and insulin were added to the perifusion medium (Earle's, pH 7.4, gassed with 95% O2/5% CO2, flow rate 50 microliters/min). When glucose was absent (in the presence of insulin 10 mU/l), LHRH release was reduced, peak levels being < 5 pg/100 microliters. The addition of glucose (100 and 300 mg/dl), in the absence of insulin, resulted in peak LHRH levels fluctuating around 35 pg/100 microliters (p < 0.05 vs. glucose 0 mg/dl). When glucose (100 or 300 mg/dl) and insulin (10 mU/l) were combined, an eightfold increase in peak LHRH values was observed, and peak levels reached 300 pg/100 microliters (p < 0.05 vs. glucose 100 and 300 mg/dl alone). In conclusion, LHRH release by perifused hypothalamic fragments is dramatically increased by low concentrations of insulin; this occurs only when glucose is available. Acutely elevated glucose levels (from 100 to 300 mg/dl) do not affect LHRH release.


Distribution of beta-endorphin immunoreactivity in the arcuate nucleus and median eminence of postpartum anestrus and luteal phase cows. Deficiency in the secretion of luteinizing hormone-releasing hormone (LHRH) from the median eminence (ME) is one of the factors limiting reinitiation of estrous cycles following parturition in cows. In previous studies, administration of naloxone, an opioid receptor antagonist, to postpartum cows increased LH secretion, suggesting that endogenous opioids inhibit the secretion of LHRH. This study employs quantitative light microscopy to describe morphological changes in the distribution of immunoreactive beta-endorphin (ir-beta-END) neurons in the hypothalamus of anestrous early postpartum (EPP, days 10-16, n = 5), midpostpartum (MPP, days 33-43, n = 4) and multiparous cycling cows (CYC, months 12-14, n = 4). Cryostat sections (60 microns) of perfusion-fixed ventral diencephalon and forebrain were immunostained with anti-beta-END serum via the biotin-avidin-peroxidase method or double stained sequentially with anti-LHRH serum, then anti-beta-END serum. In all cows, beta-END immunoreactive perikarya, mostly bipolar neurons, were located in the arcuate and periarcuate nucleus (ARC), with some perikarya in the ME. Within the ARC, the percentage area immunostained for ir-beta-END was greater (p < 0.01) for the CYC than EPP cows, with MPP intermediate but not significantly different from the other groups. Consistent for all cows, the percentage area of ir-beta-END in ventral ARC regions was greater (p < 0.05) than dorsal ARC regions. Fibers from these neurons coursed into the anterior hypothalamus, preoptic area and bed nucleus of stria terminalis. Ventrally projecting fibers entered the ME forming a densely staining band within the external layer.(ABSTRACT TRUNCATED AT 250 WORDS)


Involvement of excitatory amino acid mechanisms in gamma-hydroxybutyrate model of generalized absence seizures in rats. gamma-Hydroxybutyric acid (GHB), a naturally occurring compound which is synthesized from gamma-aminobutyric acid (GABA), induces bilaterally synchronous spike wave discharges, associated with behavioral changes, reminiscent of petit mal or generalized absence seizures in rats. In the present study, possible involvement of excitatory amino acids (EAAs) in GHB-induced spike wave discharges was investigated. The noncompetitive antagonist of NMDA receptors, MK-801, attenuated GHB-induced spike wave discharges at all doses tested (0.025-1.0 mg/kg) but dose-dependently induced suppression of EEG bursts in GHB-treated animals. The suppression of bursts was never observed with GHB in control experiments. N-Methyl-D-aspartate (NMDA) had a similar effect on GHB-induced spike wave discharges, when it was administered prior to GHB. This effect of NMDA was partially reversed by MK-801. The competitive antagonists of NMDA receptors, (+/-)CPP and CGP 43487 and the antagonist at the strychnine-insensitive glycine site, HA-966, also suppressed GHB-induced spike wave discharges with the EEG progressing to suppression of bursts but were weaker in this regard than MK-801 or NMDA. These data raise the possibility of involvement of excitatory amino acids in the GHB model of absence seizures.


Antiparkinsonian drugs memantine and trihexyphenidyl potentiate the anticonvulsant activity of valproate against maximal electroshock-induced seizures. Memantine increased the threshold for electroconvulsions, when administered at 1.0-6.0 mg/kg (i.p.) and given in subthreshold doses of 0.0156, 0.0625, 0.125 and 0.5 mg/kg (i.p.) potentiated the protective efficacy of valproate, against maximal electroshock (50 mA)-induced seizures in mice, lowering the ED50 from 235 to 197, 172, 164 and 130 mg/kg, respectively. Trihexyphenidyl, applied in doses of 30 and 50 mg/kg (i.p.), did not influence the electroconvulsive threshold per se but when combined with valproate, strongly enhanced its anticonvulsant activity against maximal electroshock-induced seizures lowering the ED50 from 206 to 103 and 46 mg/kg, respectively. The chimney test and retention testing in mice revealed that administration of memantine at 0.5 mg/kg (i.p.) or trihexyphenidyl at 30 mg/kg (i.p.) together with valproate in doses of 130 or 103 mg/kg (i.p.), respectively, resulted in motor impairment and caused impairment of long-term memory, similar to the effects of valproate alone, when applied at its ED50 against maximal electroshock. Neither memantine nor trihexyphenidyl altered the total level of valproate in plasma. It may be concluded that the potentiation of the anticonvulsant activity of valproate, by memantine and trihexyphenidyl, is not associated with a pharmacokinetic interaction.


Protection against amphetamine-induced neurotoxicity toward striatal dopamine neurons in rodents by LY274614, an excitatory amino acid antagonist. LY274614, 3SR,4aRS,6SR,8aRS-6-[phosphonomethyl]decahydr oisoquinoline-3- carboxylic acid, has been described as a potent antagonist of the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor. Here its ability to antagonize the prolonged depletion of dopamine in the striatum by amphetamine in iprindole-treated rats is reported. A single 18.4 mg/kg (i.p.) dose of (+/-)-amphetamine hemisulfate, given to rats pretreated with iprindole, resulted in persistent depletion of dopamine in the striatum 1 week later. This prolonged depletion of dopamine in the striatum was antagonized by dizocilpine (MK-801, a non-competitive antagonist of NMDA receptors) or by LY274614 (a competitive antagonist of NMDA receptors). The protective effect of LY274614 was dose-dependent, being maximum at 10-40 mgkg (i.p.). A 10 mg/kg dose of LY274614 was effective in antagonizing the depletion of dopamine in the striatum, when given as long as 8 hr prior to amphetamine but not when given 24 hr prior to amphetamine. Depletion of dopamine in the striatum was also antagonized when LY274614 was given after the injection of amphetamine; LY274614 protected when given up to 4 hr after but not when given 8 or 24 hr after amphetamine. The prolonged depletion of dopamine in the striatum in mice, given multiple injections of methamphetamine, was also antagonized dose-dependently and completely by LY274614. The data strengthen the evidence that the neurotoxic effect of amphetamine and related compounds toward nigrostriatal dopamine neurons involves NMDA receptors and that LY274614 is an NMDA receptor antagonist with long-lasting in vivo effects in rats.


Phencyclidine-induced desensitization of striatal dopamine release. Increased release of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) from slices of striatum of DBA/2J mouse in response to administration of phencyclidine (PCP) in vitro has been observed to be transient, despite continued exposure to PCP. To determine whether this transient response was a result of depletion of releasable pools, toxicity or an adaptive response (desensitization), the recovery of the response to PCP was evaluated. Slices in the control condition were exposed to PCP (300 microM) during test-exposure only. Slices in the PCP pre-exposure condition, were exposed first to PCP (30 microM; pre-exposure) and subsequently to PCP (300 microM; test-exposure). During a washout period (0, 30, 60 or 120 min) between exposures to PCP, the slices were superfused in the absence of PCP. Pre-exposure to PCP diminished the subsequent response to test-exposure to PCP (49 and 37% of control for DA and DOPAC, respectively) after 0 min washout. Overflow of DA evoked by PCP returned towards control values but remained decreased (66% of control) after up to 120 min washout. However, overflow of DOPAC did not return to control values after 60 min washout. Thus, the diminished dopaminergic response, resulting from continued exposure to PCP was not due to depletion of the releasable pool or cytotoxicity but rather to a dynamic adaptive response of the dopaminergic neuron to PCP.


Phencyclidine and auditory sensory gating in the hippocampus of the rat. The psychotomimetic drug 1-(1-phenylcyclohexyl) piperidine (PCP, phencyclidine) was found to cause a deficit in the gating of the response of the hippocampal neuron to repeated auditory stimuli, which is similar to a particular physiological feature observed in human psychosis. Other drugs, with sigma agonist and/or N-methyl-D-aspartate (NMDA) antagonist effects, were administered and their ability to cause a loss of auditory gating was compared to that of PCP. The rank order of effectiveness was levoxodrol > PCP and (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801) > N-allylnormetazocine (SKF 10047) > dexoxodrol > 3-(+/-)2-carboxypiperazine-4-yl) propyl-1-phosphonate (CPP). Further studies of two of the drugs, PCP and MK-801, showed that selective lesioning of the noradrenergic input with the neurotoxin DSP4, as well as less selective depletion of monoamines with reserpine, blocked the loss of gating. Phencyclidine, and other drugs with the same spectrum of action, most likely disrupt gating by increasing noradrenergic activity through a sigma mechanism.


Effects of halothane on membrane potential and discharge activity in pairs of bulbar respiratory neurons of decerebrate cats. In aiming to test the possibility of synaptic interactions, the effect of inhalation of halothane (2% for 90 sec) was studied on 45 out of 88 pairs of respiratory neurons, simultaneously recorded with intracellular and extracellular microelectrodes, in both sides of the ventral respiratory group of decerebrate cats. Halothane produced various effects on these respiratory neurons; namely, depolarization (n = 30) or hyperpolarization (n = 15) of intracellularly recorded neurons, an increase (n = 7) or decrease (n = 38) in the firing of extracellularly recorded neurons. However, with repeated application, the agent produced a consistent effect in a given cell. Spike-triggered averaging of synaptic noise, using spikes of non-antidromically-activated respiratory units, did not reveal any unitary postsynaptic potential but a symmetric synaptic wave of medium-frequency-oscillation (35-50 Hz) in 7 pairs. In addition, power spectral analysis of the membrane potential and spike-interval histogram of the paired neuron, displayed no correlated activity suggestive of synaptic interactions. For all the neuronal pairs examined, halothane produced random effects on their patterns of firing and synaptic waves. The present results suggest that halothane exerts a selective effect on each respiratory neuron and that the lack of a correlated response to application of halothane reflects the lack of synaptic interaction between pairs of bilaterally sampled neurons of the ventral respiratory group.


The pharmacological properties of CS-722, a newly synthesized centrally acting muscle relaxant. The pharmacological properties of (R)-4-chloro-2-(2-hydroxy-3-morpholinopropyl)-5-phenyl-4-isoxaz olin-3-one hydrochloride (CS-722), a newly synthesized, centrally acting muscle relaxant, were studied in rats. The drug CS-722 reduced the radio frequency decerebrate rigidity in a dose-dependent manner (25-100 mg/kg, p.o.); it inhibited the increase in discharges from Ia afferent fibers, gamma-motor activity, which was induced by stimulation of the reticular formation. The compound, however, showed no effect on the basal discharge of Ia afferent fibers. The polysynaptic reflex was depressed by CS-722, with less influence on the monosynaptic reflex in intact and spinal preparations and CS-722 did not prolong thiopental-induced sleeping time. In rats anesthetized with halothane, CS-722 did not affect the electroencephalogram (EEG) arousal response, which was elicited by stimulation of the reticular formation. The results of this study suggest that CS-722 can exert a muscle relaxant action, at a dose range at which depression of the ascending reticular activating system was negligible. The results also suggest that depressions of the gamma-motor system and the polysynaptic reflex may contribute to the muscle relaxant action of CS-722.


Characterization of the transcallosal response in aged rats and its susceptibility to nootropic drugs. The transcallosal response in aged rats was recorded and its susceptibility to certain nootropic drugs was compared with adult animals, under urethane-anesthesia. The transcallosal response in 24-month old rats was significantly reduced in the amplitude of both positive and negative waves, as compared with 5-month old animals. In adult rats, intravenous administration of 100 mg/kg of calcium hopantenate augmented the amplitude of both the positive and the negative waves. Intraperitoneal administration of 300 mg/kg of calcium hopantenate or 10-100 mg/kg of aniracetam increased the amplitude of the negative wave by 20-30% above the control level but had no effect on the positive one. In aged rats, these drugs, given intraperitoneally, also increased the negative wave without affecting the positive one and the degree of augmentation was more prominent; both drugs increased the amplitude of the negative wave by about 190% of the control. These results suggest that the susceptibility to the nootropic drugs became even more striking in older animals, the function in the brain of which are reduced by the natural ageing process.


Desensitization of 5-HT1A autoreceptors by chronic administration of 8-OH-DPAT. The function of 5-HT1A autoreceptors was examined by measuring the ability of the 5-HT1A receptor agonist 8-OH-DPAT to reduce 5-HT release in the striatum using in vivo microdialysis. 8-OH-DPAT reduced the release of 5-HT in the striatum. Chronic treatment with 8-OH-DPAT (1.0 mg/kg s.c.) for 7 days, but not 1 day, attenuated the effect of an acute challenge dose of 8-OH-DPAT. The results of the present study indicate that in vivo microdialysis can be used to study the effects of activation of 5-HT1A autoreceptors on 5-HT release and the regulation of 5-HT release by chronic administration of psychoactive drugs.


Intracerebral actions of the 5-HT1A agonists, 8-OH-DPAT and buspirone and of the 5-HT1A partial agonist/antagonist, NAN-190, on female sexual behavior. Proestrous rats were infused intracerebrally with 50-1000 ng 8-OH-DPAT, 500 or 2000 ng buspirone or 125-500 ng NAN-190. For each drug, bilateral infusions into the mediobasal hypothalamus inhibited female lordosis behavior and proceptivity and initiated resistive behavior. The effects of the drugs were evident within 5-20 min of infusion and generally lasted for 1-2 hr. The effective sites for 5-HT1A-mediated inhibition of sexual behavior were most concentrated in the ventromedial nucleus of the hypothalamus. Cannulae sites anterior, posterior or dorsal to the ventromedial nucleus or clearly within the IIIrd ventricle were less effective at disrupting lordosis behavior. The inhibition of sexual behavior, following 8-OH-DPAT occurred in a dose-dependent manner and appeared to include the loss of motivation of the female to mate. Buspirone produced similar, but quantitatively smaller, effects on lordosis behavior. NAN-190 slightly, but significantly, suppressed lordosis behavior after either intracerebral or intraperitoneal injection and substantially increased resistive behavior. These results suggest that the inhibition of lordosis behavior, following treatment with 5-HT1A agonists, include an action within the ventromedial nucleus. Moreover, 5-HT1A receptors in this area appear to play a functionally important role in the modulation of the female's "willingness" to mate.


Influence of repeated treatment with buspirone on central 5-hydroxytryptamine and dopamine synthesis. The anxiolytic agent buspirone was administered subcutaneously twice a day for 10 days to Sprague-Dawley rats, at a dose of 3 mg kg-1. Controls were given saline. On the eleventh day, the rats were given an injection of NSD-1015, an aromatic L-amino acid decarboxylase inhibitor, 30 min before decapitation. To another group of rats, only one injection of buspirone was given, followed 30 min later by NSD-1015. After a further 30 min the animals were decapitated. The brains were rapidly removed and the raphe nuclei, striatum, hippocampus and cerebellum were dissected out on to dry ice. With the use of HPLC, the four regions of the brain were assayed for 5-hydroxytryptophan and 3,4-dihydroxyphenylalanine, reflecting the synthesis of 5-HT and dopamine, respectively. In those rats which had received an acute dose of buspirone, the synthesis of 5-HT was substantially reduced in all four regions of the brain. However, in those rats which had received buspirone for 10 days, no such alterations in the synthesis of 5-HT were observed. The synthesis of dopamine was unchanged in any of the regions of the brain, after the acute dose of buspirone. After 10 days of treatment with buspirone, however, the synthesis of dopamine in the striatum was significantly reduced. These findings suggest that repeated treatment with buspirone reduces the synthesis of dopamine in the striatum but that the synthesis of 5-HT is unaffected.


The effects of intravenous administration of cholecystokinin on feeding behaviour and release of pituitary hormones in pigs are not mediated by serotonergic (5-HT3) receptors. Two experiments were carried out using the serotonergic (5-HT3) antagonist ondansetron (GR 38032F) to investigate whether the actions of peripherally-administered cholecystokinin octapeptide (CCK) in the prepubertal pig might involve 5-HT3 receptors. In Experiment 1, it was shown that ondansetron (10 or 30 mg, i.v.) did not affect the initial feeding response and did not modify the behavioural inhibition induced by a subsequent injection of CCK (1.3 microgram/kg, i.v.). In Experiment 2, it was demonstrated that the nauseogenic action of CCK, indicated by its stimulatory effect on release of vasopressin and cortisol, was not markedly altered by ondansetron (30 mg, i.v.). These results suggest that 5-HT3 receptors play a negligible part in mediating the behavioural and endocrine responses induced by bolus intravenous injections of CCK in this species.


4-Bromo-6-nitroquipazine: a new ligand for studying 5-hydroxytryptamine uptake sites in vivo. The present study was undertaken to evaluate 2 bromo-derivatives (4-bromo-6-nitroquipazine and 6-bromoquipazine) of quipazine as potential ligands for studying 5-hydroxytryptamine (5-HT; serotonin) uptake sites in the brain in vivo. The inhibition experiments of [3H]5-HT uptake into synaptosomes from rat brain and of the binding of [3H]6-nitroquipazine to membranes of rat brain showed that 4-bromo-6-nitroquipazine and 6-bromoquipazine were very potent and selective inhibitors of 5-HT uptake in vitro, very close to that of 6-nitroquipazine. Furthermore, 4-bromo-6-nitroquipazine was about a 2-fold more potent inhibitor of specific binding of [3H]6-nitroquipazine in vivo in the hypothalamus of mouse brain than 6-bromoquipazine. Thus, 4-bromo-6-nitroquipazine seems to be superior to 6-bromoquipazine, as a potential ligand for in vivo imaging of 5-HT uptake sites in the brain.


Effect of escalating doses of d-fenfluramine on the content of indoles in brain. The neurochemical effects of a large dose challenge (5 mg/kg, i.p.) of d-fenfluramine (d-F) in rats, given saline or gradually escalating doses of d-F (0.1-2.5 mg/kg, i.p.), were examined with regard to regional sensitivity and the time-course of recovery. The indole-depleting effect after the large dose of d-F to saline-pretreated animals appeared to differ, depending on the areas of brain considered (cortex greater than hippocampus greater than striatum), despite the fact that the drug and its main metabolite, d-norfenfluramine (d-NF) distributed almost uniformly in the regions of brain examined. The depletion in all these regions of the brain was reversible within 6 weeks, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) being back to control levels in the hippocampus and striatum but not 5-HT in the cortex. However, when rats were exposed to gradually escalating doses of d-F the recovery of indoles in the brain, after injection of the large dose challenge, appeared to be faster. Indoles were markedly less reduced 1 week later in the cortex, hippocampus and striatum, with content of indole in the striatum showing complete recovery and the long-term depletion of 5-HT and 5-HIAA, by the subsequent large dose challenge was almost completely reversed in all regions. Analysis of the concentrations of d-F and its main metabolite d-fenfluramine (d-NF) in brain excluded any pharmacokinetic tolerance. These results suggest that during therapeutic treatment with d-F, the use of escalating doses may attenuate the potential for the long-lasting decrease of 5-HT in brain.


Gliotoxic actions of excitatory amino acids. Cultures of neonatal Type I astrocytes of the rat were exposed to a series of excitatory amino acid analogs to identify those compounds that were gliotoxic. In addition to L-alpha-aminoadipate, a previously identified gliotoxin, L-homocysteate, L-serine-O-sulfate, L-alpha-amino-4-phosphonobutyrate and L-alpha-amino-3-phosphono-propionate were also found to induce a sequence of degenerative events that led to the lysis of the astrocytes. Cellular injury was assessed by quantifying the activity of lactate dehydrogenase present in the surviving astrocytes. Prior to lysis, the cells went through a succession of distinctive morphological changes, the most prominent of which involved nuclear alterations. The nuclei appeared swollen, contained "pale" or "watery" nucleoplasm and exhibited a very prominent nuclear membrane and obvious nucleoli. These astrocytes appeared quite similar in appearance to the Alzheimer's Type II astrocytes, principally associated with the pathology of hepatic encephalopathy. The nuclear anomalies, which are thought to be indicative of cellular damage and compromised function, were also produced by the endogenous transmitters L-glutamate and L-aspartate, although with time, the affected astrocytes appeared to recover and return to normal morphology, without lyzing. These findings suggest that excessive levels of excitatory amino acids may induce cellular damage to astrocytes, as well as neurons. Once damaged, the resulting reductions in astrocyte function may further contribute to CNS losses and the overall pathology attributed to the excitatory amino acids.


Nicotine-induced depolarization of cerebral cortical synaptosomes is dependent upon sodium. Earlier studies from this laboratory demonstrated that activation of nicotinic cholinergic receptors of cerebral cortical synaptosomes of the rat produced a decrease in the accumulation of [3H]tetraphenylphosphonium ([3H]TPP+) as a result of a decreased synaptosomal membrane potential. In the present study, the role of sodium in the effect of nicotine on the accumulation of [3H]TPP+ and the estimated potential difference was explored. Replacement of buffer sodium with either sucrose or N-methyl-D-glucamine (NMDG), attenuated the depolarization produced by the sodium channel activator, veratridine and had no effect on potassium-induced depolarization. The effect of nicotine on accumulation of [3H]TPP+ into cerebral cortical synaptosomes was abolished in sucrose buffer and attenuated in NMDG buffer. 1,1-Dimethyl-4-phenylpiperazinium iodide (DMP; 30 microM) produced a small increase in the influx of 22Na+ into cerebral cortical synaptosomes. The effect of DMPP on the influx of 22 Na+ was not blocked by tetrodotoxin. These results support the hypothesis that the nicotinic cholinergic receptor in the brain, functions as a sodium ionophore and further demonstrate that accumulation of synaptosomal [3H]TPP+ provides a simple tool with which to assess the effect of nicotine on sodium permeability through open nicotinic cholinergic receptor ionophores.


Involvement of cholinergic mechanisms in impairment of working memory in rats following basolateral amygdaloid lesions. In order to clarify the role of the amygdala in the working and reference memory of rats in the three-panel runway task, the effects of lesions of subnuclei of the amygdaloid complex on this behavior were studied. Rats that had been trained preoperatively, until they achieved the criterion of learning, were subjected to lesions of the amygdala. In the working memory task, lesions of the basolateral subdivision of the amygdala caused a significant increase in the number of errors (attempts to pass through two incorrect panels of the three panel-gates at four choice points), while lesions of the corticomedial amygdala had no effect on working memory errors. The increase in working errors, observed in basolateral amygdaloid-lesioned rats, declined gradually as retraining sessions were given once each day, reverting to control levels on and after the sixth session. In the reference memory task, the number of errors was not affected by lesions of the basolateral or corticomedial amygdala. The increase in working memory errors, induced by lesions of the basolateral amygdala was significantly reduced by intraperitoneal administration of the inhibitors of cholinesterase, tetrahydroaminoacridine (0.32-1.0 mg/kg) and physostigmine (0.032-0.1 mg/kg), and the muscarinic receptor agonist, oxotremorine (0.1 mg/kg), before the runway test. These findings suggest that the basolateral amygdala is selectively involved in working memory but not in reference memory and that the lowering of central cholinergic function may account for the impairment of working memory, induced by lesions of the basolateral amygdala.


Central cardiovascular effects of physostigmine in anesthetized cats. The central cardiovascular effects of a cholinesterase inhibitor, physostigmine, were studied in alpha-chloralose- and urethane-anesthetized cats, to determine the underlying site and mechanism of action. Intravenous injection of physostigmine produced a dose-dependent fall in blood pressure and heart rate. These responses were blocked by intravenous injection of atropine; however, the peripheral antimuscarinic agent, methscopolamine, failed to inhibit the depressor response. In decerebrated cats, physostigmine elicited similar responses in blood pressure and heart rate as in intact animals. In spinal cats, physostigmine failed to evoke any response. Physostigmine significantly reduced sympathetic nervous activity, as measured by renal sympathetic nerve discharges, indicating that the fall in blood pressure was due to a decrease in sympathetic tone. These results demonstrate that physostigmine, which crosses the blood-brain barrier, produces a depressor response through stimulation of muscarinic cholinergic receptors, located in the medullary region and that the effect is mediated by a decrease in sympathetic activity.


Electrophysiological correlates for antinociceptive effects of histamine after intracerebral administration to the rat. Data have been collected indicating possible functions for histamine in brain but there are only a very few data, collected exclusively with behavioural tests, about the effects of histamine on the perception of the pain, an important aspect in the homeostasis of the human body. The purpose of the present study was to investigate the effects of histamine, injected directly into the lateral cerebral ventriculi on the firing of nociceptive thalamic neurones, detected by electrophysiological techniques in rats rendered arthritic by injection of Freund's adjuvant into the left hindfoot. The noxious test stimuli used were either extension or flexion of the ankle or mild lateral pressure on the heel. With increasing doses of histamine (5, 10, 20, 40 micrograms) it was possible to observe an increasing inhibitory and long-lasting effects of the evoked activity, with a significant dose-effect linear regression. The inhibitory responses, induced by histamine, probably by a hyperpolarization phenomenon that decreased excitatory postsynaptic potentials, were clues for the presence of a histaminergic pathway in parallel with and/or in connection with other adrenergic, gabaergic, serotoninergic and opioidoergic pathways that regulate the transmission and the modulation of algogenic electrophysiological messages.


Mechanisms of spinal reflex depressant effects of CS-722, a newly synthesized centrally acting muscle relaxant, in spinal rats. The mechanisms of the depressant action of (R)-4-chloro-2-(2-hydroxy-3-morpholinopropyl)-5-phenyl-4-isoxaz olin-3-one hydrochloride (CS-722), a newly synthesized centrally acting muscle relaxant, on spinal reflexes were investigated in spinal rats. The drug CS-722 (50 mg/kg, i.v.) depressed the polysynaptic reflex but was less effective on the monosynaptic reflex. Eperisone-HCl (10 mg/kg, i.v.) and baclofen (2 mg/kg, i.v.) markedly decreased the monosynaptic and polysynaptic reflexes, with longer durations than CS-722; CS-722, eperisone and baclofen depressed the dorsal root reflex. The excitability of the motoneurone was reduced by CS-722 and eperisone. Excitability of the primary afferent fibres was reduced by CS-722, while eperisone and baclofen had no effect. Both CS-722 and eperisone did not have a depressant influence on the focal synaptic potential. These results suggest that CS-722 and eperisone but not baclofen, have a common motoneurone-membrane-stabilizing action and that this action may contribute, in part, to the spinal reflex depressant effects of CS-722 and eperisone.


Behavioral effects of atriopeptin in rats. High densities of atriopeptin-immunoreactive fibers and of highly specific and selective atriopeptin receptor sites are present in brain areas involved in animal behavior. The possible influence of these peptides on behavior was thus investigated in adult rats. The intracerebroventricular injection of atriopeptin II modified male sexual behavior (reduction in mount latency) at the dose of 5 micrograms/animal; lower and higher doses were ineffective. Open-field behavior was also modified by i.c.v. atriopeptin II at the doses of 5 and 10 micrograms/rat, which induced an increase in the number of external and internal crossings and of external rearings. Finally, in fasted rats, atriopeptin II, at the dose of 10 micrograms/rat, significantly increased the amount of food intake 30 and 60 min after injection. These findings indicate that atriopeptins may modify different animal behaviors.


Neurotensin increases extracellular striatal dopamine levels in vivo. This study employed intracranial microdialysis to assess the effects of neurotensin (NT) infusion on extracellular dopamine (DA) and DA metabolite concentrations in the rat striatum and nucleus accumbens, and the effects of NT on alterations in extracellular DA levels induced by cocaine and the DA D-2 receptor agonist, quinpirole. Direct NT infusion (.10, 1.0, 10.0 microM) did not significantly affect extracellular DA in the nucleus accumbens, but did produce a significant increase in the DA metabolite homovanillic acid (HVA). In contrast, direct NT infusion produced an increase in striatal DA levels, without altering DA metabolites. Neurotensin infusion (.10 microM) into the striatum significantly attenuated the peak DA increase induced by an intraperitoneal (IP) injection of a low dose (10.0 mg/kg) but not a high dose (30.0 mg/kg) of cocaine. Neurotensin infusion (.10 microM) did not affect the decrease in DA and its metabolites induced by an IP injection of a low dose of quinpirole (.03 mg/kg), but did alter the decrease in HVA induced by a high dose of quinpirole (.10 mg/kg). These results suggest that NT differentially affects in vivo DA release in the striatum and nucleus accumbens, and further strengthens the assertion that NT is an important modulator of dopaminergic function.


Neuropeptide Y-containing interneurons in the hippocampus receive synaptic input from median raphe and GABAergic septal afferents. Neuropeptide Y has been extensively studied in the central nervous system due to a possible involvement of neuropeptide Y-containing neurons in cognitive functions. In the hippocampus neuropeptide Y is present in a subpopulation of nonpyramidal cells, which control the firing of hippocampal output neurons. In the present study we examined whether septohippocampal and raphe-hippocampal afferents--known to have a powerful effect on hippocampal electrical activity patterns--innervate neuropeptide Y-containing neurons in the hippocampal formation of the rat. Using a combination of pre- and postembedding immunostaining and tracing with Phaseolus vulgaris leucoagglutinin (PHAL) we showed that GABAergic afferents arising from the medial septal area extensively innervate neuropeptide Y-containing neurons. Afferents of median raphe origin, most of which are thought to be serotonergic, were also found to make multiple synaptic contacts with these cells. Thus, the neuropeptide Y-containing subpopulation of interneurons--which innervate distal dendrites of principal cells--are also among those through which different subcortical nuclei modulate information processing in the hippocampal formation.


Microsurgical removal of petroclival meningiomas: a report of 33 patients. This is a report of 33 consecutive cases of petroclival meningioma treated surgically at our institution over the last 10 years; there were 21 women and 12 men between the ages of 27 and 68 (mean age, 52). All patients were assessed by computed tomographic scans including coronal sections and bone algorithm studies; in most cases, digital subtraction angiography and magnetic resonance imaging were also done. The largest tumor diameter was between 2 and 3.5 cm in 14 cases, 3.5 to 6 cm in 15 cases, and over 6 cm in 4 cases. Dural attachment predominantly involved the clivus and apical petrous bone on one side only; in 14 cases, however, the tumor grew over the clivus midline or crossed the tentorial notch. Cranial nerve deficit was extant in all cases and was commensurate with tumor size. Cerebellar signs and somatic motor deficits were present in 60 and 30% of cases, respectively. The surgical approaches used were the retromastoid-retrosigmoid in 23 cases, subtemporal in 5 cases, and combined retromastoid subtemporal presigmoid in the remaining 5. Total removal was achieved in 26 cases (79%); incomplete removal occurred in 7 cases (21%). The extent of tumor removal and operative morbidity were not significantly related to tumor size. Brain stem indentation, arterial and cranial nerve encasement, and epidural invasion were the main factors that prevented total tumor removal and influenced operative morbidity. There was no intraoperative mortality, but three patients (9%) died perioperatively. In the postoperative period, most patients went through momentary neurological deterioration, chiefly due to new cranial nerve deficits. The average follow-up was 4.3 years in 27 patients; of these 17 were unchanged and 10 were improved. Before surgery, only 13 patients were self-sufficient; at long-term follow-up, another 6 had achieved independence. Our experience suggests that, even though real petroclival meningiomas still represent a formidable surgical challenge, such tumors can in most cases be removed completely with low attendant mortality and acceptable morbidity.


Tumor control after stereotactic radiosurgery in neurofibromatosis patients with bilateral acoustic tumors. During a 4-year interval, 17 patients with bilateral acoustic tumors (vestibular schwannomas) underwent unilateral stereotactic radiosurgery using a multisource gamma unit; 2 patients underwent radiosurgery of both tumors in separate sessions. Eleven patients with unoperated contralateral tumors served as concurrent controls to compare the effects of radiosurgery with the natural history of acoustic tumors. After radiosurgery, the tumor control and regression rates were 89.5 and 21.1%, respectively (median neuroimaging follow-up, 1.4 years; range, 0.3-3.9). The tumor regression rate increased to 40% for patients evaluated at least 12 months after radiosurgery. In comparison to the unoperated contralateral tumors, stereotactic radiosurgery achieved tumor control, as assessed by the ultimate change in tumor size at follow-up (P, 0.012), the change in tumor size over time (P, 0.006), and tumor growth rates (P, 0.003). This study provided convincing evidence that tumor stabilization after radiosurgery (as assessed by neuroimaging) truly represented tumor control. The incidence of delayed facial neuropathy after radiosurgery compared favorably with the incidence reported after microsurgical removal. Some hearing was preserved in one-third of the patients who had preoperative hearing, including three patients who were contralaterally deaf. Stereotactic radiosurgery should be considered as a primary surgical modality for many patients with neurofibromatosis Type II.


Flow cytometric analysis of deoxyribonucleic acid ploidy and proliferation in choroid plexus tumors. The deoxyribonucleic acid (DNA) content of 10 choroid plexus tumors, including 4 malignant tumors and 3 normal choroid plexus controls, was analyzed by flow cytometry to determine whether a ploidy or proliferation rate is a better predictor of tumor behavior than histological features. Nine of 10 neoplasms had both diploid and aneuploid modal populations. One neoplasm and all three control cases had only a diploid peak. Among the tumors, the DNA indices of the aneuploid peaks ranged from 1.1 to 2.2. The percentage of aneuploid cells ranged from 7 to 99, and no distinction was made between benign and malignant. Proliferation rates were estimated from the combined S-phase fractions (SPF). The mean SPF of the control group was 0.7% +/- 0.15% SD. The mean SPF of the benign tumors (1.1 +/- 0.82% SD) was significantly different from the malignant group (7.0 +/- 1.25% SD; range, 5.3 to 8.6%) P = 0.0095. Low SPF fractions always correlated with favorable outcome. Higher proliferation rates were generally associated with an aggressive course. Evaluation of proliferation rates may help predict the behavior of choroid plexus tumors, particularly when histological features are equivocal. Measurement of DNA ploidy does not appear to have a role in the evaluation of choroid plexus tumors.


Diffuse arteriovenous malformations: a clinical, radiological, and pathological description. In a review of our series of patients with arteriovenous malformations (AVMs), a group with atypical angiographic and histopathological characteristics was discovered. Unlike the typical AVM, these lesions contained normal cerebral tissue between the abnormal vessels. We call these lesions diffuse AVMs, and think that this AVM represents one end of the AVM spectrum from a tight nidus to a diffuse lesion. The mean age of these patients was 18.1 years. Eight patients presented with an intracerebral hemorrhage, two with seizures, one with headache without hemorrhage, and one with ischemic symptoms compatible with vascular steal. Cerebral angiography revealed three AVMs to be 2 to 4 cm in diameter, four were 4 to 6 cm in diameter, and five were > 6 cm in diameter. Characteristic angiographic features included multiple small arterial feeders, small ectatic vessels in the malformation itself, multiple small draining veins, and a diffuse, puddling appearance of the contrast dye. Despite 16 operations in 11 patients, complete resection of the AVM was accomplished in only 8. The four patients with residual disease have received radiation therapy. Histopathology of the surgical specimens found AVM vessels interspersed among normal appearing neurons and white matter. Leptomeningeal angiodysplasia was noted when the cerebral cortex was involved. Gliosis was noted in some cases. Diffuse AVMs represent a difficult surgical challenge and recognition of the lesion aids in surgical planning.


Children with cerebral venous thrombosis diagnosed with magnetic resonance imaging and magnetic resonance angiography. From 1985 to 1991, 13 children were diagnosed at the University of Illinois College of Medicine at Peoria, Saint Francis Medical Center, with cerebral venous thrombosis (CVT) by magnetic resonance imaging scan. Ages ranged from newborn to 5 years. Six children were premature neonates, five were term neonates and two were 5 years old. In the premature neonates, thrombosis was usually associated with other problems. All the term neonates had seizures. In all neonates, thrombosis resolved without any specific treatment. In the two older children, one presented with pseudotumor cerebri and one with coma. These children required neurosurgical intervention. Follow-up magnetic resonance imaging scans were obtained in 9 of 13 children and showed thrombus resolution in each case. Three children were studied in the acute and convalescent stages by magnetic resonance angiography using time-of-flight techniques. Each follow-up magnetic resonance angiogram showed improvement in venous flow consistent with their clinical course and other imaging studies. We conclude that 1) CVT in children encompasses a range of clinical conditions which may or may not require neurosurgical intervention; 2) magnetic resonance imaging is superior to other modalities for the diagnosis of CVT; and 3) magnetic resonance angiography is an alternative means to monitor the evolution of CVT and efficacy of therapeutic intervention.


Hemodynamic effects of preoperative embolization in cerebral arteriovenous malformations: evaluation with transcranial Doppler sonography. A series of 83 patients with cerebral arteriovenous malformations is presented. All patients were evaluated with transcranial Doppler sonography. Thirty-two patients were treated with staged embolization and surgery: 19 of these patients were operated on within 4 weeks of the last embolization, and the remaining 13 patients underwent surgery 6 months or more from embolization. Transcranial Doppler sonography performed 1 day after embolization showed a significant (> 60%) reduction of main feeder flow velocity in 72% of patients after the first embolization and in 45% of patients after the second embolization. In no case did such a significant reduction occur after the third embolization. A flow redistribution in the basal vessels (defined as an increase in flow velocity of at least 30% of the initial value) occurred only in patients after the first embolization (64%). On delayed post-embolization studies, complete recovery of flow velocity in the embolized vessel occurred in 46% of patients, and sonographic recruitment of new feeders occurred in the remaining 54%. When main feeder flow velocity (mean) was higher than 120 cm/s after embolization and before surgery, the incidence of postoperative hyperemic complications (cerebral edema and/or intracerebral hematoma) was significantly higher than in patients with a mean flow velocity under 120 cm/s. It is concluded that transcranial Doppler sonography is a valuable method for a noninvasive hemodynamic assessment of shunt flow in arteriovenous malformations, and it permits a physiological monitoring of hemodynamic changes after embolization and allows more precise indications regarding further stages of embolization and timing of surgery after embolization.


The Maudsley Mentation test: a method for extended monitoring of mental status after aneurysmal subarachnoid hemorrhage. A new scale for the repeated, rapid assessment of mental function in patients with subarachnoid hemorrhage is described. Its reproducibility is evaluated and early experience with its use in the intended clinical setting is reported. The test (Maudsley Mentation Test) proved to be more sensitive to fluctuations in cerebral functioning than existing measures of conscious level, and the results were reproducible among observers with different backgrounds (surgeons, nurses, and psychologists). The results suggest a relationship between performance on mentation testing and quality of outcome. The Maudsley Mentation Test is thought to offer a suitable measure with which to monitor patients during the acute phase of their illness to supplement clinical assessment and provide evidence of deterioration at an early stage. It is also potentially useful as an end point in acute protection and treatment studies.


Total intravenous anesthesia for improvement of intraoperative monitoring of somatosensory evoked potentials during aneurysm surgery. Two anesthetic regimens for monitoring somatosensory evoked potentials (SEPs) during intracranial aneurysm surgery were compared. Eighty-four sequential cases of intracranial aneurysms were operated on employing SEP monitoring. The first group of 22 cases was anesthetized with "balanced anesthesia" and the second group of 62 cases received total intravenous anesthesia (TIVA) consisting of propofol and alfentanil. In the TIVA group, the amplitude of early cortical SEP responses (N20-P25, or P40-N50) was significantly higher than that of responses in the balanced anesthesia group. In median nerve SEPs, the averaged amplitude of N20-P25 was 3.22 microV with TIVA and 1.69 microV with balanced anesthesia (P = 0.006). Similarly, posterior tibial nerve SEPs showed a P40-N50 response of 1.85 microV and 1.00 microV, respectively (P = 0.017). The superior signal-to-noise ratio obtained with TIVA allowed more frequent and reliable intraoperative SEP recordings than was possible with balanced anesthesia, resulting in rapid and reliable feedback for the surgeon. In 19% of median nerve SEPs recorded with TIVA, the cortical responses were over 5 microV in amplitude, so that reproducible N20-P25 responses were obtainable by averaging only 10 to 50 serial responses, that is, two to three recordings per minute. The higher amplitude of posterior tibial nerve SEPs recorded with TIVA made monitoring during surgery for anterior communicating artery aneurysms possible in all cases. This was not always the case with balanced anesthesia. The late deflection of median nerve SEPs (N30) was more frequently observed with TIVA.(ABSTRACT TRUNCATED AT 250 WORDS)


Continuous-pressure controlled, external ventricular drainage for treatment of acute hydrocephalus--evaluation of risk factors. Experience with a continuous-pressure controlled, external ventricular drainage system (EVD) in 100 patients (n = 49 female, n = 51 male; mean age, 56.3 yr) with acute hydrocephalus is reported. Cerebrospinal fluid circulation disturbances resulted from hemorrhages caused by subarachnoid hemorrhage (n = 45), parenchymal hemorrhages from angioma (n = 4), anticoagulants (n = 7), or hypertension or other reasons (n = 30); in addition, hydrocephalus developed from infections (n = 3), tumors (n = 2), infratentorial infarction (n = 5), or unknown reasons (n = 4); 52 patients had ventricular hemorrhages. No patient died of system-associated morbidity. Mean time of EVD treatment was 9.5 days, with 40 patients being treated for 10 to 29 days; routine refobacin (5 mg) flushing of the system was performed three times a day. Patients without cerebrospinal fluid leakage had a 2% rate of secondary infection compared with 13% in patients with cerebrospinal fluid leakage due to ventricular catheter placement (P < 0.05; overall infection rate, 5%). A clinical mortality rate of 29% during EVD treatment was observed in subarachnoid hemorrhage patients (Hunt and Hess Grades II, III, IV, and V; n = 9, 9, 18, and 9, respectively); recurrent hemorrhages during EVD treatment occurred in 19 patients (26 hemorrhages), and of these, 10 patients died. System occlusion was seen in 19 cases (12 of 45 patients with subarachnoid hemorrhage), requiring catheter and system renewal in 1 case; system extraction was seen in 3 cases, misplacement was seen in 11 cases, and disconnection was seen in 5 cases.(ABSTRACT TRUNCATED AT 250 WORDS)


Penetrating stab wounds to the brain: the timing of angiography in patients presenting with the weapon already removed. Angiography is always necessary in patients with penetrating stab wounds to the head, to exclude unexpected vascular lesions. The most important, since they are seldom clinically evident, are traumatic aneurysms and arteriovenous fistulae. It has previously been proposed that carotid angiography should be delayed until the start of the second week, to allow for better visualization of these complications. However, traumatic aneurysms can rupture at any time after the injury, and the mortality resulting from a second hemorrhage is unacceptably high. A prospective study was undertaken in which 330 patients with penetrating stab wounds to the head underwent angiography as soon as possible after admission. In 250 of these patients (76%), the weapon had already been removed by the assailant, and there was radiological evidence of penetration of the dura. Of these 250, 130 patients underwent angiography within 7 days of the injury. Another 51 patients, who presented late, underwent angiography more than 7 days after the injury. The timing of angiography did not affect the identification of traumatic aneurysms, the incidence of which was 12% in both groups. Of the patients with cranial stabs and who required urgent evacuation of intracerebral hematomas, 10% had traumatic aneurysms that could be dealt with simultaneously. No patient in this series suffered a secondary hemorrhage. We conclude that it is neither necessary nor safe to delay angiography. In some patients, either because of vasospasm or "cut-off" of a vessel, a second angiogram may be necessary to further elucidate a vascular abnormality that might not have been evident originally.


Syringomyelia in Chiari malformation: relation to extent of cerebellar tissue herniation. In 47 patients with Chiari malformations (41 with Type I, 6 with Type II) diagnosed by magnetic resonance imaging, syringomyelia was found significantly more frequently in those who had a herniation of 9 to 14 mm (9 of 16, 56%) than in those who had a smaller (2 of 15, 13%) or larger (2 of 16, 13%) herniation. Syringomyelia associated with the Chiari malformation is generally considered to be due to mechanical factors induced by altered cerebrospinal fluid hydrodynamics. On the basis of the present study, one may speculate whether these mechanical factors affect the cord most efficiently at an intermediate level of herniation, which may prove to be a risk factor for the development of syringomyelia.


Monitoring of brain tissue pressure with a fiberoptic device. Continuous monitoring of brain tissue pressure can now be achieved with intracerebral placement of fiberoptic microtransducers. This study was undertaken to test the safety, accuracy, and reliability of this relatively new type of intracranial pressure (ICP) monitoring. Initially, the fiberoptic device was compared with a concurrently functioning intraventricular catheter in 18 patients. The results from the two methods corresponded closely over a wide range of pressures, and the correlation coefficient approached 1.0. Subsequently, this monitor was used for routine measurement of ICP in a series of almost 200 neurosurgical patients at risk of intracranial hypertension. The tracings showed good wave forms and consistent absolute values of ICP. No instances of hemorrhage, mechanical failure, or other complications were associated with this monitor, except one case of infection, which was not directly attributable to the device per se. When bilateral intraparenchymal pressures were recorded in patients with unilateral mass lesions, significant transitory pressure differentials between the ipsilateral and contralateral sides were documented. It is concluded that monitoring intraparenchymal pressure with the fiberoptic device offers safe and reliable ICP recordings for routine neurosurgical practice. In patients with unilateral masses, ICP should be measured in close proximity to the lesion.


Protection of iodine-125 brachytherapy brain injury in the rat with the 21-aminosteroid U-74389F. Radiation protection was studied in a rat brachytherapy brain injury model. Radiation lesions were produced by stereotactic placement of high-activity iodine-125 seeds on the frontal lobe of F-344 rats. A minimum dose of 80 Gy was delivered to a 5.5-mm-radius volume. Radiation damage was evaluated 24 h after removal of the seeds by T1-weighted gadolinium-enhanced magnetic resonance imaging on a 1.5-T unit. Computerized three-dimensional reconstruction of the lesions seen on magnetic resonance imaging was performed to calculate the volume of radiation injury. Two experiments were performed with rats of different weights (mean, 300 g; mean, 180 g). All animals underwent surgical placement of an indwelling internal jugular catheter before brachytherapy. Treated animals received the 21-aminosteroid U-74389F 5 mg/kg intravenously every 6 hours during the implant and for 24 hours after the removal of the iodine-125 seed. Control animals were administered vehicle only. In both experiments, a statistically significant reduction in volume of radiation damage was observed in the U-74389F-treated group compared with the control group.


The effect of the 21-aminosteroid U74006F in a rabbit model of thromboembolic stroke. U74006F, a novel 21-aminosteroid, is an inhibitor of iron-dependent lipid peroxidation that is devoid of glucocorticoid and mineralocorticoid side effects. The efficacy of U74006F in reducing cerebral infarct size was investigated in a rabbit model of thromboembolic stroke. Each animal received either U74006F (3.0 mg/kg immediately before and 2 hr after embolization, n = 8) or vehicle control (n = 10). Hematocrit, mean arterial pressure, PCO2, PO2, and pH were measured and controlled both before and after the administration of an autologous clot into one internal carotid artery. Regional cerebral blood flow (in ml/100 g/min, mean +/- SEM) measured by hydrogen clearance was similar in both groups, being reduced from 68.2 +/- 9.6 to 5.2 +/- 1.9 in the control group immediately after clot embolization and from 73.3 +/- 14.9 to 7.0 +/- 1.7 in the U74006F group. Four hours after embolization the brain was harvested and cerebral infarct size was determined using the triphenyl-tetrazolium chloride technique (% hemisphere, mean +/- SEM). In the U74006F-treated group, the infarct size was significantly reduced (P < 0.05) to 14.8 +/- 6.4 from a control value of 36.0 +/- 6.4. Additionally, cerebral blood flow values after embolization were consistently higher in the U74006F group, although the differences were not statistically significant. This data suggests that the 21-aminosteroid U74006F may have a protective effect in cerebral ischemia.


Regional changes in central nervous system thyrotropin-releasing hormone after pentylenetetrazol-induced seizures in dogs. We have recently shown that seizures induce significant and sustained elevations of thyrotropin-releasing hormone (TRH) in specific extrahypothalamic rat brain regions associated with epileptic foci including amygdala, hippocampus, pyriform cortex, and anterior cortex. Seizures were induced in dogs to further study the effect on central nervous system TRH in a species known to show epileptiform seizures. Adult mongrel beagles were given pentylenetetrazol (PTZ) to induce generalized tonic-clonic seizures. Two groups of dogs were given either PTZ or saline every other day for four intravenous injections. Major motor seizures were observed visually and by electroencephalography with each PTZ injection, and these lasted from 3 to 10 minutes. Forty-eight hours after the fourth seizure, the dogs were killed and brains were removed, dissected, and stored at -90 degrees. After acetic acid extraction, extracts were assayed for TRH content by specific radioimmunoassay. Significant (P < 0.05) postictal TRH increases were seen in frontal cortex (1.5-fold), dorsal hippocampus (2.2-fold), pyriform cortex (2.5-fold), and amygdala (2.1-fold). Cerebellum, medulla, thalamus, hypothalamus, and septum showed no postictal changes in TRH. This report is the first to demonstrate TRH elevations in specific central nervous system regions associated with epileptic foci in the dog. Our results continue to stress the importance of the pyriform/periamygdaloid region as a key limbic region of endogenous TRH action in response to seizures and provides further evidence that TRH is either directly or indirectly involved in seizure modulation. Additional recent data from our laboratory and others suggest that this modulation is intrinsic to the hippocampus and may be anticonvulsant in nature.


Gender distribution and sidedness of middle fossa arachnoid cysts: a review of cases diagnosed with computed imaging. According to earlier reports, arachnoid cysts seem to occur more frequently in males, and on the left side. The latter phenomenon could, however, be explained by a greater significance attributed to symptoms from the dominant hemisphere as a justification for invasive procedures in the pre-computed tomography era. The literature from the last third of the era of computed tomography is reviewed with respect to gender distribution and sidedness for middle fossa arachnoid cysts. Also included are a few cases of our own from the same period. It is evident from this survey of the literature, based on computed tomography studies, that there is a significant tendency for these cysts to occur in males, with a male/female ratio of nearly 3:1. This preponderance toward males could not be explained by the somewhat higher frequency of associated subdural hematomas that was found in male patients. The survey also showed that middle fossa arachnoid cysts occur or are detected significantly more frequently on the left side than on the right, with a ratio of 1.8:1.


Meningeal melanocytoma: diagnostic criteria for a rare lesion. A case of meningeal melanocytoma, the 14th in the literature, is presented. Neurodiagnostic imaging, with both computed tomographic scan and magnetic resonance imaging, is included. Pathological examination of the tumor consisted of light microscopy, electron microscopy, and immunohistochemistry. The literature is reviewed and pathological criteria are presented to distinguish meningeal melanocytoma from meningiomas containing melanin pigment and from malignant melanoma.


Metastatic carcinoid tumor to the orbit and brain. Carcinoid tumors constitute an uncommon source of metastatic lesions to the brain. We report the case of a 63-year-old man who initially sought treatment for proptosis 15 years before coming to our attention with a metastatic intracerebral left parietal carcinoid. The pathological features of the exenterated orbital mass were interpreted as undifferentiated carcinoma, and a lesion of the left lower lobe of the lung that had been removed 6 years earlier had been reported as metastatic malignant melanoma. The long duration between the initial diagnosis and the onset of neurological symptoms brought into question the original diagnosis, which, in retrospect, was most consistent with metastatic carcinoid. Staining for cytokeratin, neuron-specific enolase, and synaptophysin in the absence of staining for S-100 and HMB-45 supported the revised pathological diagnosis. Metastatic intracerebral carcinoid from an unrecognized bronchogenic source is a rare event, particularly after an orbital metastasis, but should be suspected when the clinical course is inconsistent with the more common causes of metastatic disease.


Chondrosarcoma of the temporal bone in an infant: case report and review of the literature. Cranial chondrosarcomas are rare. The majority of cases arise from the base of the skull and are most common in adult life. In this report, an infant with a chondrosarcoma of the temporal bone is discussed. We are not aware of a previously reported case of chondrosarcoma of the temporal bone in this age group.


Meningeal melanocytoma of the C8 nerve root: case report. A case of a meningeal melanocytoma involving the C8 nerve root is presented. The clinical symptoms and the radiological investigations resembled a neurinoma of the spinal nerve root. Intraoperatively the tumor was seen to be firmly attached to the dural covering of the dorsal nerve root. By using microsurgical technique, complete removal of the tumor with preservation of the ventral nerve root was accomplished. Histological examination revealed a typical meningeal melanocytoma as described by Limas and Tio in 1972. Ten additional cases of previously reported spinal meningeal melanocytomas are reviewed. The importance of differentiating this benign lesion from meningeal malignant pigmented tumors is stressed.


Ependymoma of the spinal nerve root: case report. Ependymomas are the most common intramedullary tumor of the spinal cord. They are most common at the region of the cauda equina, accounting for up to 90% of primary tumors in that area. Extraspinal ependymomas are rare. We describe a case of an ependymoma arising in a spinal peripheral nerve root.


Langerhans cell histiocytosis of the spine causing cord compression: case report. A case of Langerhans cell histiocytosis of the spine causing myeloradiculopathy is reported. Almost complete regression of symptoms and signs was observed in the patient after surgical treatment and radiotherapy. The clinical and histological features of the disease are discussed. The literature dealing with the previously reported cases of spinal histiocytosis involving neural structures is reviewed.


Anomalous muscle belly of the flexor digitorum superficialis associated with carpal tunnel syndrome: case report. A patient had a 10-year history of pain and swelling in the right wrist and palm. Carpal tunnel exploration showed anomalous muscle bellies of flexor digitorum superficialis II and III. The muscle bellies were excised. Postoperatively, the symptoms disappeared. Our case is compared with others in the literature.


Outcome measures for clinical trials involving traumatically brain-injured patients: report of a conference. A conference was held in Houston, Texas, on October 8-9, 1991, to develop recommendations for outcome measures for clinical trials in traumatic brain injury. Participants, all experts in this area, discussed and agreed on treatments for patients with severe brain injury (Glasgow Coma Score [GCS] < or = 8) and moderate brain injury (GCS, 9-12). A parallel trial design was recommended rather than a factorial, sequential, or crossover design. It was agreed that stratifying randomization based on motor score alone or on a combination of motor score and age would result in increased power. Acute stage measurements, such as cerebral blood flow, cerebrospinal fluid biochemistry, and evoked potentials, were recommended only when they satisfied a specific hypothesis. Functional outcome measures were recommended as the primary outcome measure for severe brain injury (GCS, 3-8). Either the Glasgow Outcome Scale or Disability Rating Scale, measured at 6 months after injury, were recommended as the primary outcome measure for severe brain injury (GCS, < or = 8). For patients with moderately severe brain injury (GCS, 9-12), the Disability Rating Scale at 3 months after injury was recommended as the primary outcome measure. The Neurobehavioral Rating Scale appears to be a satisfactory instrument for measuring behavioral changes. Specific neuropsychological measures were recommended as supplementary outcome measures for both severe and moderate brain injury, consistent with a 1.5-hour period available for testing.


Skill learning and repetition priming in Alzheimer's disease. While perceptual-motor learning occurs normally in Alzheimer's disease (AD) patients, their ability to acquire the skill of reading transformed text has not been well delineated. AD patients and matched controls were timed as they read two blocks of words presented in mirror image. Control subjects displayed both skill learning and repetition priming, whereas AD patients displayed only repetition priming. Skill learning in AD patients was associated with their ability to complete verbal analogies. They displayed the expected impairment in recognition for the words from the mirror reading task. The failure of AD patients to acquire the mirror reading skill can be understood through a task analysis and may reflect an underlying deficit in abstract reasoning that precludes the development of appropriate pattern analyzing strategies needed to transform rotated text.


Effect of stimuli in right hemispace on left-sided neglect in a line cancellation task. Twenty-seven patients with right cerebral infarcts resulting in left-sided neglect in a line cancellation task were also tested for line cancellation when the lines were confined to the left half of sheets. All but one patient (whose neglect in the former condition was minimal) were still impaired in the latter condition, a finding that indicates that hyperattraction to test stimuli in the unneglected (right) hemispace was not the crucial factor preventing them from completing the standard version of the cancellation task, although it may have played some role. The results are consistent with the conclusion that hyperattention to stimuli in the unneglected hemifield, and possibly to stimuli in the unneglected hemispace, together with other factors, could account for the patients' impairment in line cancellation.


Judgements about numerosity by a commissurotomized subject. A commissurotomized subject, L.B., was shown asterisks flashed at random locations, up to four in each field, and attempted either to compare the numbers in the two fields or to report the total number. The main results were: (a) Report was more accurate with unilateral than with bilateral presentation, suggesting that the difficulty integrating across fields was partly attentional; (b) in integrating across fields, attention was focused on one field, with only crude 'one-or-many' information from the other; (c) in cross-field comparisons, the focus was on the LVF, but in reporting the number it was on the RVF when report was oral or right-handed, and on the LVF when report was left-handed; (d) cross-field comparisons were improved when the locations were mirrored across the midline.


Prehension movements directed to approaching objects: influence of stimulus velocity on the transport and the grasp components. In this investigation we studied the influence of object velocity on the transport and on the grasp components of prehension movements directed to approaching objects. Three experiments were carried out. In the first experiment six subjects were required to reach and grasp a sphere that approached them with a constant velocity. The effects of four velocities were studied. The results showed that the end point of the arm movement changed with object velocity: nearer the body with higher than with lower object velocities. Transport velocity increased with movement amplitude and the deceleration phase decreased in duration with higher object velocities. On the contrary the grasp component was not affected by object velocity. The second experiment was a control experiment carried out in order to verify whether a possible influence of object velocity on the grasp could be revealed in an experimental condition in which grasp planning relies without doubt on visual computation of all object features. In this experiment object velocity and object size were randomly varied. The results showed that the grasp was not influenced by object velocity, whereas it was sensitive to changes of object size. The third experiment had the two-fold aim of establishing (1) whether transport velocity was influenced by object velocity once the location in space at which the object had to be grasped was fixed and (2) whether the grasp kinematics differed for prehension movements directed respectively to stationary or to moving objects. Results showed that the first part of the transport is affected only by distance, whereas the deceleration phase decreased with increasing object velocity. This last result suggests that subjects minimized object displacements in order to grasp the sphere correctly. The grasp component differed between the conditions of stationary and moving stimuli only in the relative timing between finger aperture and closure phases. The closure phase decreased in the condition of moving stimuli. The results of the three experiments indicate the dependence of transport parameters on object velocity, whereas grasp parameters appear to be unaffected.


Acquisition and transfer of declarative and procedural knowledge by memory-impaired patients: a computer data-entry task. Previous research demonstrated that a single amnesic patient could acquire complex knowledge and processes required for the performance of a computer data-entry task. The present study extends the earlier work to a larger group of brain-damaged patients with memory disorders of varying severity and of various etiologies and with other accompanying cognitive deficits. All patients were able to learn both the data-entry procedures and the factual information associated with the task. Declarative knowledge was acquired by patients at a much slower rate than normal whereas procedural learning proceeded at approximately the same rate in patients and control subjects. Patients also showed evidence of transfer of declarative knowledge to the procedural task, as well as transfer of the data-entry procedures across changes in materials.


Assessment of attention and memory efficiency in persons with solvent neurotoxicity. Memory and attention were evaluated in 40 persons with a history of organic solvent exposure and 40 demographically similar controls. Exposed subjects, in comparison to controls, had reduced digit spans, were deficient at learning new information, and recall on a Brown-Peterson distractor test was especially low following a 30-sec interference interval. If original learning was considered, long-term recall was similar for both groups. On a test of sustained attention, the Continuous Performance Test, exposed subjects became less accurate over successive blocks, a pattern opposite to that seen in control subjects. The data suggest that the memory impairment following solvent exposure may result from deficient allocation of attentional resources due to the inability to deal effectively with an increase in processing load.


Interhemispheric interaction affected by computational complexity. The present study investigated whether dividing information between the hemispheres becomes more advantageous to task performance as computational complexity increases. We hypothesized that interhemispheric processing would benefit performance especially for computationally complex tasks, whereas it would hinder performance for relatively simple ones. A letter-matching task was given to 23 subjects at three levels of computational complexity. Complexity was varied either by increasing the number of inputs to be processed or by the nature of the decision to be made. The results indicated that each of these manipulations of complexity influenced performance by making it more advantageous to have both hemispheres involved in processing rather than just one. Furthermore, the effects of each manipulation were separable.


Intact implicit memory in patients with frontal lobe lesions. Patients with frontal lobe lesions and control subjects were administered tests of word-stem completion priming. In this implicit memory test, subjects are first presented words (e.g. MOTEL, PARADE) in an incidental learning paradigm. Following word presentation, subjects are shown word stems (e.g. MOT, PAR) and asked to produce the first word that comes to mind. Patients with frontal lobe lesions exhibited normal levels of word-stem completion. These findings indicate that implicit memory can operate normally despite damage to the prefrontal cortex. The present results substantiate previous neuropsychological and positron emission tomography findings which indicate that word priming depends critically on posterior cortical areas.


Peptidergic modulation of learning a motoric food-procuring conditioned reflex skill. Experimental data are presented which were obtained during an investigation of the influence of various doses of a synthetic heptapeptide based on tafcine on the learning of a complex instrumental skill in dogs. The effectiveness of the intranasal application of the peptide in the early stages of learning was demonstrated, as was its capacity to restore the lost skill. The vegetative support of the motoric reactions during the modulation of the learning by the peptide was investigated.


Dynamics of interstimulus intervals in the activity of neurons of the sensorimotor cortex during the development of a food-procuring reflex in the rabbit. The impulse activity of neurons of the sensorimotor cortex (SMC) during the formation of a food-procuring reflex in the rabbit, as well as in trained animals if reinforcement is discontinued and substituted, was investigated. In the process of training the neurons of the SMC acquire the capacity for anticipatory reactions. The sudden abolition and substitution of reinforcement elicits the appearance of activity which is characteristic for the process of discordance in the acceptor of the result of the action. Repeated substitutions lead to the appearance of activity which is characterized by a coordination process at the moment of the "recognition" of the substitution, despite the absence of food reinforcement.


Active electrogenesis of command neurons of defense behavior of the snail during conditioning. A change in the active electrogenesis of command neurons of the defensive closing of the spiracle of the edible snail during the development, extinction, and repeat development of a classical conditioned defense reflex in response to tactile stimulation is described in this study; the tactile stimulation of another point of the body served as the differential stimulus. As the biological significance of the conditional stimulus increased as the result of training, the excitability of the command neurons in response to this stimulus increased. At the same time, the neurons manifested reduced excitability in response to the differential stimulus. The possible mechanisms of the rapid reorganization of the excitability of the neurons and the functional significance of the change in the generation threshold of the AP are discussed.


Structure and nature of macrophages participating in the wallerian degeneration of nerve fibers. The posttraumatic processes of Wallerian degeneration of nerves have been illuminated in detail. The dynamics of the breakdown of axons and the myelin sheaths of nerve fibers has been established, as have been the periods of the changes in the composition of myelin, and the reactive changes in the Schwann cells and the connective tissue structures in the makeup of the nerve as well as the formation of "foam" cells have been described. The controversial questions which have been raised in these studies regarding the role of the cellular elements (the Schwann cells, the endoneurial fibroblasts, the cells of the epi- and perineurium) during Wallerian degeneration remain unresolved until the present time. In particular, the question as to which cells participate in the cleanup of the products of the breakdown of the myelin sheaths, and as to the character of the inflammatory infiltration in Wallerian degeneration and the degree of the participation of the various cellular elements in the destructive and reparative processes, has not been elucidated. Some investigators believe that the Schwann cells accomplish the cleanup of the products of the breakdown of the myelin sheaths. There are also data suggesting that the macrophages are of considerable significance in the cleanup of the products of the breakdown of nerve fibers of both the PNS and the CNS following their injury. It has been demonstrated by means of monoclonal antibodies to macrophages, radioautography, and immunocytochemical methods that these macrophages have a hematogenous origin.(ABSTRACT TRUNCATED AT 250 WORDS)


Influence of pulse stimulation of the visual cortex on the function of the superior colliculus of the awake rabbit. It has been demonstrated in awake rabbits that stimulation of the visual cortex by a solitary pulse of electrical current leads to the formation of a short-latency response in the superior colliculus. The formation of this response is suppressed when a light stimulus precedes it. At the same time, a conditioning solitary electrostimulation of the visual cortex induces a short inhibition of the formation of the response to the test light stimulus. This fact suggests that the influences of the visual cortex on the functioning of the superior colliculus may be biphasic in character. When the adrenergic apparatus of the reticular formation is blocked this inhibitory influence bears a more pronounced and prolonged character. The stimulation of the reticular formation, on the other hand, by means of anodic polarization leads to the diametrically opposite effect: the inhibitory character of the influence of the cortex is replaced by a facilitatory one. The inference is drawn that the character and the directionality of the influence of the visual cortex on the functioning of the superior colliculus is determined to a significant degree by the initial functional state of nonspecific brain systems.


Features of the behavioral reactions of rats during exposure to constant electrical fields of varied intensities. The dynamics of the spontaneous orienting-motoric activity and the character of the formation and of the extinction of conditioned reflex reactions during food and painful reinforcement in rats following exposure to a constant electrical field (CEF) with an intensity of from 30 to 160 kV/m were studied. It was established that as the result of the exposure to a CEF of relatively low intensity, orienting activity intensifies, and the formation and the extinction of the conditioned avoidance reaction slow down. In the presence of the effect of a CEF of medium intensity, an increase in activity in the vertical plane correlates with the rapid formation of the defense reflex and the prolonged maintenance of the conditioned reactions developed. In the presence of a high-intensity field the number of both horizontal and vertical locomotions decreases due to an increase in the proportion of static elements and grooming. The rate of formation of the conditioned reflexes with food and painful reinforcement slows sharply.


A microdialysis investigation of the release of norepinephrine in the hypothalamus induced by 2-deoxyglucose in awake rats. The level of norepinephrine in the extracellular space of the lateral hypothalamus was measured by means of intracerebral microdialysis in awake rats. The introduction of desipramine (10 mumole) into the perfusing medium did not affect the basal level of norepinephrine, but increased the release of norepinephrine during local K(+)-stimulation. Neuroglycopenia created under the influence of 500 mg/kg of 2-deoxyglucose induced a threefold increase in the level of norepinephrine in the extracellular space of the hypothalamus, which achieved a maximal value in the first 40 min following the introduction of the substance, and thereafter gradually decreased to the basal level.


Magnetic resonance imaging and histopathology of cerebral gliomas. The correlation of magnetic resonance imaging (MRI) with histopathological findings was analysed in 26 patients with untreated cerebral gliomas. In low-grade gliomas, T2-weighted images demonstrated relatively homogeneous high-intensity lesions involving both the grey and the white matter. In high-grade gliomas, especially grade IV, T2-weighted images demonstrated prominent heterogeneity in signal intensity, which consisted of a hyperintense "core", less hyperintense or normal intensity "rim" and surrounding finger-like areas of high intensity. Marked and irregular contrast enhancement was evident in all but one case of these high-grade gliomas in which gadolinium-DTPA was used. Histological examination revealed tumour cells extending as far as the borders of the high-intensity areas shown on T2-weighted images in both high- and low-grade gliomas, but in 5 of 8 low-grade and 4 of 18 high-grade gliomas, isolated tumour cells extended beyond the hyperintense areas shown on T2-weighted images.


Volume measurement of multiple sclerosis lesions with magnetic resonance images. A preliminary study. The ability to visualise multiple sclerosis lesions in vivo with magnetic resonance imaging suggests an important role in monitoring the course of the disease. In order to help the long-term assessment of prospective treatments, a semi-automated technique for measuring lesion volume has been developed to provide a quantitative index of disease progression. Results are presented from a preliminary study with a single patient and compared to measurements taken from lesion outlines traced by a neuroradiologist, two neurologists and a technician. The semi-automated technique achieved a precision of 6% compared to a range of 12-33% for the manual tracing method. It also reduced the human interaction time from at least 60 min to 15 min.


Marchiafava-Bignami disease: serial changes in corpus callosum on MRI. Serial MRI findings of changes in corpus callosum lesions in two cases of Marchiafava-Bignami disease are presented. In both, MRI displayed diffuse swelling of the corpus callosum in the acute stage, thought to represent oedema and demyelination. In the chronic stage, in addition to atrophy of the corpus callosum with presumed focal necrosis, previously undescribed focal hypointensity on T2-weighted images, of unknown cause, was observed in the corpus callosum.


Tay-Sachs disease: progression of changes on neuroimaging in four cases. The neuroradiological findings in four patients with Tay-Sachs disease are described in three phases of the clinical course. The basal ganglia and cerebral white matter show low density on computed tomography and high signal intensity on T2-weighted magnetic resonance imaging in the initial phase. The caudate nuclei are characteristically enlarged and protrude into the lateral ventricles in the first and second phases. The cerebral white matter shows low density on the CT which varies in extent from the second to third phases, and the whole brain becomes atrophic in the last phase. Thus, central nervous system involvement in the disease may begin in basal ganglia as well as in cerebral white matter.


Neuropsychological correlates of brain atrophy in Huntington's disease: a magnetic resonance imaging study. Magnetic resonance imaging and a comprehensive cognitive evaluation were carried out in a series of 29 patients with mild to moderate Huntington's disease (HD). A factor analysis of the neuropsychological test scores provided three factors: a memory/speed-of-processing factor, a "frontal" factor, and a response inhibition factor. The memory/speed factor correlated significantly with measures of caudate atrophy, frontal atrophy, and atrophy of the left (but not the right) sylvian cistern. There were no significant correlations between the "frontal" or response inhibition factors and measures of cortical or subcortical brain atrophy. Our findings confirm that subcortical atrophy is significantly correlated with specific cognitive deficits in HD, and demonstrate that cortical atrophy also has important association with the cognitive deficits of patients with HD.


MRI of herpes simplex encephalitis.

MRI of herpes simplex encephalitis. The magnetic resonance imaging (MRI) findings in eight patients with herpes simplex meningoencephalitis were reviewed: 14 examinations were analysed. The most striking finding was high signal intensity in the temporal lobe(s) with the typical configuration known from CT. Meningeal enhancement after Gd-DTPA administration was clearly seen in four patients. Haemorrhagic changes are much better seen on MRI than on CT. When adequate motion control can be achieved, MRI becomes the examination of choice in the diagnosis and follow-up of herpes simplex encephalitis. Localized 1H MR spectroscopy also proved promising in the study of neuronal loss.


Isodense subdural haematomas on CT:MRI findings. MRI findings are described in two patients with subdural haematomas isodense on CT. In one patient, admitted 6 weeks after trauma, a chronic subdural haematoma showed extreme hypointensity on T2-weighted images, suggesting acute trauma, and therefore acute rebleeding. In the second patient with severe anaemia, an acute subdural haematoma was hyperintense on T2-weighted images, suggesting chronic trauma; this may be explained by the low haematocrit and a possible mixture of blood with cerebrospinal fluid. The MRI features of subdural haematomas and hygromas have to be kept in mind, in order not to misjudge the age of the haematoma.


Infarction in the territory of the anterior inferior cerebellar artery: report of five cases. The clinical and MRI features were correlated in five cases of infarction in the territory of the anterior inferior cerebellar artery. The lateral portion of the pons area was affected in four cases, the middle cerebellar peduncle in two, and the cerebellar hemisphere in three. The lesion was restricted to the cerebellar hemisphere in one patient. In no case did the clinical features conform to the classical description.


Retrograde filling of the anterior choroidal artery: vertebral angiographic sign of obstruction in the carotid system. Retrograde filling of seven anterior choroidal arteries from the posterior circulation was observed on a vertebral angiogram in six patients with occlusion of the proximal anterior choroidal artery or of the internal carotid artery. In one patient with thrombotic occlusion of the internal carotid artery, the enlarged anterior choroidal artery functioned as a major collateral pathway from the posterior circulation to the territory of the middle cerebral artery. Retrograde filling of the anterior choroidal artery is a sign of obstruction changes in the ipsilateral carotid artery at or proximal to the origin of the anterior choroidal artery.


Safety of the adjustable pressure ventricular valve in magnetic resonance imaging: problems and solutions. We performed magnetic resonance imaging in 30 patients with hydrocephalus with Sophy adjustable pressure valves (PAVS). A pressure check following the MRI study showed a significant proportion with pressure valve changes, which could easily be readjusted by percutaneous manipulation. The value of the PAVS and its safety during MRI examinations are discussed.


Cortical region of interest definition on SPECT brain images using X-ray CT registration. We present a method for brain single photon emission computed tomography (SPECT) analysis based on individual registration of anatomical (CT) and functional (133Xe regional cerebral blood flow) images and on the definition of three-dimensional functional regions of interest. Registration of CT and SPECT is performed through adjustment of CT-defined cortex limits to the SPECT image. Regions are defined by sectioning a cortical ribbon on the CT images, copied over the SPECT images and pooled through slices to give 3D cortical regions of interest. The proposed method shows good intra- and interobserver reproducibility (regional intraclass correlation coefficient approximately 0.98), and good accuracy in terms of repositioning (approximately 3.5 mm) as compared to the SPECT image resolution (14 mm). The method should be particularly useful for analysing SPECT studies when variations in brain anatomy (normal or abnormal) must be accounted for.


Effects of radiotherapy determined by 11C-methyl-L-methionine positron emission tomography in patients with primary cerebral malignant lymphoma. Two cases of histologically proven primary cerebral malignant lymphoma were examined serially with positron emission tomography (PET) using 11C-methyl-L-methionine (11C Met). Lesions delineated by 11C Met accumulation extended beyond enhancing areas on either X-ray computed tomography (CT) or magnetic resonance imaging. High uptake of 11C Met accurately showed biologically active and residual tumours, at a time when disappearance of a contrast-enhancing lesion on CT seemed to indicate involution. PET provides valuable information on the extent of tumour and assessment of radiotherapy in malignant lymphoma.


Aspergillosis of the paranasal sinuses.

Aspergillosis of the paranasal sinuses. The CT appearances of 13 cases of pathologically proven aspergillosis involving paranasal sinuses were reviewed. Symptoms included rhinorrhea, nasal obstruction, headache, facial pain and foul smell from the nose. At operation, these lesions appeared yellowish, brownish, grey or black in colour, and contained dirty or muddy material. Microscopic examination of the tissue removed showed an Aspergillus ball with chronic inflammation but without invasion of the nasal or sinus mucosa in 6 cases, and tissue invasion with necrosis and inflammation in 7. The structures involved, in order of frequency, were: maxillary sinus, nasal cavity, ethmoid sinus, orbit and cavernous sinus. The orbit was involved in 2 cases, therefore categorized as invasive; the other 11 cases were non-invasive as judged by CT. Calcification was seen in the lesions of 9 cases. In most cases the adjacent bony structures showed areas of erosion and sclerosis. Aspergillosis should be suspected in the presence of a mass in the paranasal sinuses or nasal cavity with calcification within it, which may not appear solid or dense and is separate from the walls of the sinus.


Ascending pharyngeal artery-internal jugular vein fistula complicating radical neck dissection. Arteriovenous fistulae of the ascending pharyngeal artery (AP) and internal jugular vein (IJ) are rare. Only two spontaneous AP-IJ fistulae have been described previously, both of which presented with pulsatile tinnitus. A unique case of an AP-IJ fistula developing after radical neck dissection is described in which the clinical presentation was identical to that of a carotid-cavernous fistula.


Chronic post-traumatic erosion of the skull base. Delayed post-traumatic erosion of the skull base is reported in three patients who presented as adults with cerebrospinal fluid fistulae and a history of recurrent meningitis. These skull defects were associated with herniation of the subarachnoid space into the diploe of the skull base, the paranasal sinuses and the orbit. This rare complication of head injury is assumed to have occurred as the result of a dural tear at the time of trauma. Its site probably determines whether a resulting meningocele widens the intradiploic space or broaches the cranial floor.


Formation of an olfactory glomerulus: morphological aspects of development and organization. We have studied the development of olfactory nerves in the rat from their first contact with the telencephalic vesicle until the formation of glomerular structures in the olfactory bulb at early postnatal period. The study is based on serial semithin and ultrathin sections of material prepared for electron microscopy and antibodies to label radial glial cells, glial fibrillary acidic protein and Rat-401. Beginning on embryonic day 12, developing olfactory axons from the olfactory placode are accompanied by migratory cells, also derived from the olfactory placode, that reach the prospective olfactory bulb by embryonic day 13. The mass of migratory cells accumulate superficial to the telencephalic vesicle. The cells increase in number by mitotic divisions. The majority of these cells represent precursor elements that will later develop into the ensheathing cells of the olfactory nerves and olfactory nerve layer of the adult. Some migratory cells penetrate into the prospective olfactory bulb early during development. The first synaptic contacts of olfactory axons with dendritic processes in the olfactory bulb were observed at embryonic day 18. Glomerular formation is initiated by penetration of cells from the migratory mass into the prospective glomerular layer by embryonic day 20 to postnatal day 0. These cells form walls surrounding zones of high synaptic density forming protoglomeruli. Postnatally, the peripheral processes of radial glial cells branch profusely delimiting glomerular formations and transform into periglomerular astrocytes. Rat-401 stains radial glial cells from embryonic day 14. Immunoreactivity becomes restricted to the olfactory glomeruli during the first postnatal weeks and it virtually disappears by the end of the first postnatal month. We conclude that the early penetration of cells from the migratory mass into the prospective olfactory bulb, observed immediately after the first synaptic contacts were established, initiates the formation of olfactory glomeruli which becomes completed by the transformation of radial glial cells into periglomerular astrocytes.