Mitochondrial Division Inhibitor 1 Prevents Early-Stage Induction of Mitophagy and Accelerated Cell Death in a Rat Model of Moderate Controlled Cortical Impact Brain Injury
First author:Niu Fei
Corresponding author:Liu Baiyun
2018-11-12
Journal:World Neurosurgery
Publication type: Original Article
IF(IF): 2.104
PMID: 30439527 Link To Pubmed Full text Download
Mitophagy and the role of Drp1 in this process after CCI were examined using Western blotting, electron microscopy, double immunofluorescence staining, neurological severity scores, and hematoxylin and eosin staining. Statistical analysis was performed using 1-way analysis of variance, followed by the least significant difference test or the Games-Howell test.
The findings from the present study support the hypothesis that Drp1-dependent mitochondrial fission contributes to mitophagy in TBI, and further understanding of the regulatory mechanisms of Drp1 will provide opportunities to develop novel strategies against TBI.
The rats exposed to CCI exhibited induction of mitophagy and fragmentation of mitochondria. When fission was blocked with Mdivi1, the mitochondria became excessively long and interconnected. Inhibition of Drp1 blocked the induction of mitophagy specifically, which aggravated neurological manifestations and neuronal apoptosis. Mdivi1 activated caspase-3 and caspase-9, implying that selective degradation of damaged mitochondria by autophagy markedly decreased cell apoptosis induced by TBI and, thus, promoted cell survival.