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J Stroke Cerebrovasc Dis · Jul 2014
Mdivi-1 prevents apoptosis induced by ischemia-reperfusion injury in primary hippocampal cells via inhibition of reactive oxygen species-activated mitochondrial pathway.
- Jinying Wang, Peng Wang, Shuhong Li, Shilei Wang, Yu Li, Nan Liang, and Min Wang.
- Medical College of Qingdao University, Qingdao, Shandong Province, China.
- J Stroke Cerebrovasc Dis. 2014 Jul 1;23(6):1491-9.
AbstractApoptosis is one of the major mechanisms of neuronal injury during ischemic-reperfusion (I/R). Mitochondrial division inhibitor (mdivi-1) is a selective inhibitor of mitochondrial fission protein Drp1. The previous experiments support that mdivi-1 reduce I/R injury in the heart model of rat, but the neuroprotective effect of the mdivi-1 is not yet clearly defined at the cellular levels in brain. In our present study, we estimated a brain model of I/R injury in vitro by subjecting oxygen and glucose deprivation (OGD) followed by reoxygenation to the cultured rat primary hippocampal cells, which aimed to find the neuroprotective mechanism of mdivi-1. The cell was pretreated with mdivi-1 for 40 minutes and then ischemia for 6 hours followed by reperfusion for 20 hours. The redox state, cell apoptosis, and expression of Drp1, Bcl-2, Bax, and cytochrome C proteins were measured. The data showed that administration of mdivi-1 at the doses of 50 μM significantly reduced oxidative stress, attenuated cell apoptosis, upregulated Bcl-2 expression, and downregulated Drp1, Bax, and cytochrome C expression. The results suggested that mdivi-1 protected brain from OGD reperfusion injury, which through suppressing the ROS initiated mitochondrial pathway. Copyright © 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.
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