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A selective inhibitor of Drp1, mdivi-1, acts against cerebral ischemia/reperfusion injury via an anti-apoptotic pathway in rats.

Abstract
Mitochondrial division inhibitor (mdivi-1) is a derivative of quinazolinone that acts as a selective inhibitor of a mitochondrial fission protein Drp1. A previous study demonstrated that as a selective inhibitor of Drp1, mdivi-1 has a protective effect in an experimental model of heart ischemia/reperfusion injury. In this study, we investigated the protective effects of mdivi-1 on cerebral ischemia/reperfusion injury in a middle cerebral artery occlusion mouse model. We found that mdivi-1 (1.2mg/kg) significantly reduced cerebral damage induced by ischemia/reperfusion. This neuroprotective effect was dose-dependent. Mdivi-1 treatment blocked apoptotic cell death in cerebral ischemia/reperfusion injury, and significantly decreased the expression of Drp1 and Cytochrome C. These results suggest that mdivi-1 exerts neuroprotective effects against nerve injury after cerebral ischemia/reperfusion, and the underlying mechanism may be through the prevention of Cytochrome C release and suppression of the mitochondrial apoptosis pathway.
AuthorsNing Zhang, Shilei Wang, Yu Li, Lei Che, Qin Zhao
JournalNeuroscience letters (Neurosci Lett) Vol. 535 Pg. 104-9 (Feb 22 2013) ISSN: 1872-7972 [Electronic] Ireland
PMID23313133 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCrown Copyright © 2013. Published by Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • 3-(2,4-dichloro-5-methoxyphenyl)-2-sulfanyl-4(3H)-quinazolinone
  • Neuroprotective Agents
  • Quinazolinones
  • RNA, Messenger
  • Cytochromes c
  • Dnm1l protein, rat
  • Dynamins
Topics
  • Animals
  • Apoptosis (drug effects)
  • Brain (drug effects, metabolism, pathology)
  • Brain Ischemia (drug therapy, etiology, pathology)
  • Cytochromes c (genetics, metabolism)
  • Dynamins (antagonists & inhibitors, genetics, metabolism)
  • Infarction, Middle Cerebral Artery (complications)
  • Male
  • Neurons (drug effects, pathology)
  • Neuroprotective Agents (pharmacology, therapeutic use)
  • Quinazolinones (pharmacology, therapeutic use)
  • RNA, Messenger (metabolism)
  • Rats
  • Rats, Wistar
  • Reperfusion Injury (drug therapy, etiology, pathology)

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