Trauma-induced cell swelling in cultured astrocytes
Arumugam R. Jayakumar, K. V.Rama Rao, Kiran S. Panickar, M. Moriyama, P. V.B. Reddy, Michael D. Norenberg
Brain edema and associated increased intracranial pressure are major consequences of traumatic brain injury that account for most early deaths after traumatic brain injury. An important component of brain edema after traumatic brain injury is astrocyte swelling (cytotoxic edema). To examine the pathophysiologic mechanisms of trauma-induced astrocyte swelling, we used an in vitro fluid percussion trauma model. Exposure of cultured rat astrocytes to 5 atm of pressure resulted in significant cell swelling at 1 to 24 hours posttrauma that was maximal at 3 hours. Because oxidative/nitrosative stress, mitochondrial permeability transition (mPT), and mitogen-activated protein kinases (MAPKs) have been implicated in astrocyte swelling in other neurologic conditions, we examined their potential roles in this model. We previously showed increased free radical generation after in vitro trauma and show here that trauma to astrocytes increased the production of nitric oxide. Trauma also induced mPT and increased phosphorylation (activation) of MAPKs (extracellular signal-regulated kinase 1/2, c-Jun-N-terminal kinase, and p38-MAPK); these changes were diminished by antioxidants and the nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester. Antioxidants, N-nitro-l-arginine methyl ester, the mPT inhibitor cyclosporin A, and inhibitors of MAPKs all significantly diminished trauma-induced astrocyte swelling. These findings demonstrate that direct mechanical injury to cultured astrocytes brings about cell swelling, and that blockade of oxidative/nitrosative stress, mPT, and MAPKs significantly reduce such swelling.
https://doi.org/10.1097/NEN.0b013e31816fc9d4
Cell cultures
Cell swelling
Cytotoxic edema
Mitochondrial permeability transition
10.1097/NEN.0b013e31816fc9d4
Dive into the research topics of 'Trauma-induced cell swelling in cultured astrocytes'. Together they form a unique fingerprint.
Astrocytes Medicine & Life Sciences 100%
Mitochondrial Transmembrane Permeability-Driven Necrosis Medicine & Life Sciences 89%
Mitogen-Activated Protein Kinases Medicine & Life Sciences 61%
Traumatic Brain Injury Medicine & Life Sciences 45%
Nitrosative Stress Medicine & Life Sciences 42%
arginine methyl ester Medicine & Life Sciences 39%
Brain Edema Medicine & Life Sciences 34%
Jayakumar, A. R., Rao, K. V. R., Panickar, K. S., Moriyama, M., Reddy, P. V. B., & Norenberg, M. D. (2008). Trauma-induced cell swelling in cultured astrocytes. Journal of Neuropathology and Experimental Neurology, 67(5), 417-427. https://doi.org/10.1097/NEN.0b013e31816fc9d4
Jayakumar, Arumugam R. ; Rao, K. V.Rama ; Panickar, Kiran S. ; Moriyama, M. ; Reddy, P. V.B. ; Norenberg, Michael D. / Trauma-induced cell swelling in cultured astrocytes. In: Journal of Neuropathology and Experimental Neurology. 2008 ; Vol. 67, No. 5. pp. 417-427.
@article{ec52b157b91d4fa69d892f3b297dd927,
title = "Trauma-induced cell swelling in cultured astrocytes",
abstract = "Brain edema and associated increased intracranial pressure are major consequences of traumatic brain injury that account for most early deaths after traumatic brain injury. An important component of brain edema after traumatic brain injury is astrocyte swelling (cytotoxic edema). To examine the pathophysiologic mechanisms of trauma-induced astrocyte swelling, we used an in vitro fluid percussion trauma model. Exposure of cultured rat astrocytes to 5 atm of pressure resulted in significant cell swelling at 1 to 24 hours posttrauma that was maximal at 3 hours. Because oxidative/nitrosative stress, mitochondrial permeability transition (mPT), and mitogen-activated protein kinases (MAPKs) have been implicated in astrocyte swelling in other neurologic conditions, we examined their potential roles in this model. We previously showed increased free radical generation after in vitro trauma and show here that trauma to astrocytes increased the production of nitric oxide. Trauma also induced mPT and increased phosphorylation (activation) of MAPKs (extracellular signal-regulated kinase 1/2, c-Jun-N-terminal kinase, and p38-MAPK); these changes were diminished by antioxidants and the nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester. Antioxidants, N-nitro-l-arginine methyl ester, the mPT inhibitor cyclosporin A, and inhibitors of MAPKs all significantly diminished trauma-induced astrocyte swelling. These findings demonstrate that direct mechanical injury to cultured astrocytes brings about cell swelling, and that blockade of oxidative/nitrosative stress, mPT, and MAPKs significantly reduce such swelling.",
keywords = "Astrocytes, Cell cultures, Cell swelling, Cytotoxic edema, Mitochondrial permeability transition, Mitogen-activated protein kinases, Nitric oxide, Oxidative stress, Traumatic brain injury",
author = "Jayakumar, {Arumugam R.} and Rao, {K. V.Rama} and Panickar, {Kiran S.} and M. Moriyama and Reddy, {P. V.B.} and Norenberg, {Michael D.}",
doi = "10.1097/NEN.0b013e31816fc9d4",
Jayakumar, AR, Rao, KVR, Panickar, KS, Moriyama, M, Reddy, PVB & Norenberg, MD 2008, 'Trauma-induced cell swelling in cultured astrocytes', Journal of Neuropathology and Experimental Neurology, vol. 67, no. 5, pp. 417-427. https://doi.org/10.1097/NEN.0b013e31816fc9d4
Trauma-induced cell swelling in cultured astrocytes. / Jayakumar, Arumugam R.; Rao, K. V.Rama; Panickar, Kiran S.; Moriyama, M.; Reddy, P. V.B.; Norenberg, Michael D.
In: Journal of Neuropathology and Experimental Neurology, Vol. 67, No. 5, 05.2008, p. 417-427.
T1 - Trauma-induced cell swelling in cultured astrocytes
AU - Jayakumar, Arumugam R.
AU - Rao, K. V.Rama
AU - Panickar, Kiran S.
AU - Moriyama, M.
AU - Reddy, P. V.B.
AU - Norenberg, Michael D.
N2 - Brain edema and associated increased intracranial pressure are major consequences of traumatic brain injury that account for most early deaths after traumatic brain injury. An important component of brain edema after traumatic brain injury is astrocyte swelling (cytotoxic edema). To examine the pathophysiologic mechanisms of trauma-induced astrocyte swelling, we used an in vitro fluid percussion trauma model. Exposure of cultured rat astrocytes to 5 atm of pressure resulted in significant cell swelling at 1 to 24 hours posttrauma that was maximal at 3 hours. Because oxidative/nitrosative stress, mitochondrial permeability transition (mPT), and mitogen-activated protein kinases (MAPKs) have been implicated in astrocyte swelling in other neurologic conditions, we examined their potential roles in this model. We previously showed increased free radical generation after in vitro trauma and show here that trauma to astrocytes increased the production of nitric oxide. Trauma also induced mPT and increased phosphorylation (activation) of MAPKs (extracellular signal-regulated kinase 1/2, c-Jun-N-terminal kinase, and p38-MAPK); these changes were diminished by antioxidants and the nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester. Antioxidants, N-nitro-l-arginine methyl ester, the mPT inhibitor cyclosporin A, and inhibitors of MAPKs all significantly diminished trauma-induced astrocyte swelling. These findings demonstrate that direct mechanical injury to cultured astrocytes brings about cell swelling, and that blockade of oxidative/nitrosative stress, mPT, and MAPKs significantly reduce such swelling.
AB - Brain edema and associated increased intracranial pressure are major consequences of traumatic brain injury that account for most early deaths after traumatic brain injury. An important component of brain edema after traumatic brain injury is astrocyte swelling (cytotoxic edema). To examine the pathophysiologic mechanisms of trauma-induced astrocyte swelling, we used an in vitro fluid percussion trauma model. Exposure of cultured rat astrocytes to 5 atm of pressure resulted in significant cell swelling at 1 to 24 hours posttrauma that was maximal at 3 hours. Because oxidative/nitrosative stress, mitochondrial permeability transition (mPT), and mitogen-activated protein kinases (MAPKs) have been implicated in astrocyte swelling in other neurologic conditions, we examined their potential roles in this model. We previously showed increased free radical generation after in vitro trauma and show here that trauma to astrocytes increased the production of nitric oxide. Trauma also induced mPT and increased phosphorylation (activation) of MAPKs (extracellular signal-regulated kinase 1/2, c-Jun-N-terminal kinase, and p38-MAPK); these changes were diminished by antioxidants and the nitric oxide synthase inhibitor N-nitro-l-arginine methyl ester. Antioxidants, N-nitro-l-arginine methyl ester, the mPT inhibitor cyclosporin A, and inhibitors of MAPKs all significantly diminished trauma-induced astrocyte swelling. These findings demonstrate that direct mechanical injury to cultured astrocytes brings about cell swelling, and that blockade of oxidative/nitrosative stress, mPT, and MAPKs significantly reduce such swelling.
KW - Astrocytes
KW - Cell cultures
KW - Cell swelling
KW - Cytotoxic edema
KW - Mitochondrial permeability transition
KW - Mitogen-activated protein kinases
KW - Traumatic brain injury
U2 - 10.1097/NEN.0b013e31816fc9d4
DO - 10.1097/NEN.0b013e31816fc9d4
Jayakumar AR, Rao KVR, Panickar KS, Moriyama M, Reddy PVB, Norenberg MD. Trauma-induced cell swelling in cultured astrocytes. Journal of Neuropathology and Experimental Neurology. 2008 May;67(5):417-427. https://doi.org/10.1097/NEN.0b013e31816fc9d4