Selective brain hypothermia ameliorates focal cerebral ischemia-reperfusion injury via inhibiting Fis1 in rats

Abstract

Mitochondrial immoderate fission induces neuronal apoptosis following focal cerebral ischemia-reperfusion (I/R) injury. With fewer complications, selective brain hypothermia (SBH) is considered an effective treatment against neuronal injury after stroke. However, the specific mechanism by which SBH influences mitochondrial fission remains unknown. Mitochondrial fission 1 protein (Fis1), a key factor of the mitochondrial fission system, regulates mitochondrial dynamics. This study aimed to investigate whether SBH regulates Fis1 expression in focal cerebral I/R injury. In this study, rat middle cerebral artery occlusion (MCAO) models were established. After 2 h of occlusion, cold saline or normal saline was pumped into rats in different groups through the carotid artery, followed by restoration of blood perfusion. Cortical and rectal temperatures showed that the cold saline treatment achieved SBH. Cerebral I/R injury increased neurological deficit scores (NDS); neuronal apoptosis; Fis1 protein and mRNA expression; cytosolic cytochrome c (cyto-Cyto c) protein expression at 6, 24 and 48 h postreperfusion; and cerebral infarct volumes at 24 h postreperfusion. Interestingly, SBH inhibited Fis1 protein and mRNA expression, blocked cyto-Cyto c protein expression, preserved neuronal cell integrity, and reduced neuronal apoptosis. However, normal saline treatment rarely resulted in positive outcomes. Based on these results, SBH inhibited Fis1 expression, thus ameliorating focal cerebral I/R injury in rats.