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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Blood-Brain Barrier, Brain Edema, Calpain, Cathepsin B, Cerebral Hemorrhage, Cysteine Proteinase Inhibitors, Drug Evaluation, Preclinical, Enzyme Activation, Enzyme Induction, Evans Blue, Extravasation of Diagnostic and Therapeutic Materials, Infarction, Middle Cerebral Artery, Leucine, Male, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Matrix Metalloproteinase Inhibitors, Nerve Tissue Proteins, Neuroprotective Agents, Premedication, Rats, Rats, Sprague-Dawley, Reperfusion, Single-Blind Method.
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Does cathepsin and calpain inhibitor E64d attenuate matrix metalloproteinase-9 activity after focal cerebral ischemia in rats? Context: Matrix metalloproteinases (MMPs) and cysteine proteases (calpain and cathepsin B) play an important role in cell death and are upregulated after focal cerebral ischemia. Because there is a significant interaction between MMP-9 with calpain and cathepsin B, we investigated the role of E64d (a calpain and cathepsin B inhibitor) on MMP-9 activation in the rat focal ischemia model. Male Sprague-Dawley rats were subjected to 2 hours of middle cerebral artery occlusion by using the suture insertion method followed by 22 hours of reperfusion. In the treatment group, a single dose of E64d (5 mg/kg IP) was administrated 30 minutes before the induction of focal ischemia, whereas the nontreatment group received dimethyl sulfoxide only. The neurological deficits, infarct volumes, Evans blue extravasation, brain edema, and MMP-9 activation in the brain were determined. Pretreatment with E64d produced a significant reduction in the cerebral infarction volume (353.1+/-19.8 versus 210.3+/-23.7 mm3) and the neurological deficits. Immunofluorescence studies showed MMP-9, calpain, and cathepsin B activation colocalized to both neurons and the neurovascular endothelial cells after ischemia, which was reduced by E64d.
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These results suggest that E64d treatment provides a neuroprotective effect to rats after transient focal cerebral ischemia by inhibiting the upregulation of MMP-9. Final Decision: yes