Administration of mitochondrial fusion promoter during ischemia and at the onset of reperfusion exert neuroprotective effects in rats with cardiac ischemia/reperfusion injury

Abstract

AbstractBackgroundAcute myocardial infarction (AMI) is one of the fetal cardiovascular diseases and a leading cause of death (1, 2). Our previous study demonstrated that pretreatment of mitochondrial fusion promoter (M1) provided neuroprotective effects on the brain following cardiac ischemia/reperfusion (I/R) injury (3). However, the effects of M1 given during ischemia and M1 given at the onset of reperfusion on brain pathologies following cardiac I/R have never been investigated.MethodSixteen male Wistar rats were randomly divided into either a sham‐operation (n = 8) or cardiac I/R (n = 24). In the cardiac I/R group, rats were then randomly divided into 3 subgroups, including the I/R operation with vehicle (0.9% sodium chloride solution for 15 minutes before I/R protocol, intravenous (i.v.) injection), the I/R operation with M1 administration during cardiac ischemia (2 mg/kg, 15 minutes after left anterior descending (LAD) coronary artery ligation, i.v. injection), and the I/R operation with M1 administration at the onset of reperfusion group (2 mg/kg at the beginning of reperfusion, i.v. injection). At the end of experimental protocol, rats were sacrificed and brains were obtained for further molecular investigation.ResultThe results demonstrated that cardiac I/R increased brain inflammation, caused microglial dysmorphology, caused brain mitochondrial dysfunction, increased tau hyperphosphorylation, and increased brain apoptosis (p<0.05, Figure 1). M1 given during ischemia and M1 given at the onset of reperfusion effectively attenuated brain pathologies following cardiac I/R by preserving microglial morphology, improving brain mitochondrial function, decreasing tau hyperphosphorylation, and decreasing brain apoptosis (p<0.05, Figure 1). Interestingly, M1 given during ischemia had better efficacy to suppressing brain inflammation, when compared to M1 given at the onset of reperfusion apoptosis (p<0.05, Figure 1).ConclusionThese findings suggest the administration of mitochondrial fusion promoter effectively decreased brain pathologies following cardiac I/R. The administration of mitochondrial fusion promoter during ischemia had greater suppression on brain inflammation than administration at the onset of reperfusion. The novel findings obtained from the present study provided the therapeutic strategies which can be translated into clinical settings for cardiac I/R injury.