An apoptosis inhibitor suppresses microglial and astrocytic activation after cardiac ischemia/reperfusion injury

Abstract

Objective: Microglial hyperactivation and apoptosis were observed following myocardial infarction and ischemia reperfusion (I/R) injury. This study aimed to test the hypothesis that the apoptosis inhibitor, Z-VAD, attenuates microglial and astrocytic hyperactivation and brain inflammation in rats with cardiac I/R injury. Materials and methods: Rats were subjected to either sham or cardiac I/R operation (30 min-ischemia followed by 120-min reperfusion), rats in the cardiac I/R group were given either normal saline solution or Z-VAD at 3.3 mg/kg via intravenous injection 15 min prior to cardiac ischemia. Left ventricular ejection fraction (% LVEF) was determined during the cardiac I/R protocol. The brain tissues were removed and used to determine brain apoptosis, brain inflammation, microglial and astrocyte morphology. Results: Cardiac dysfunction was observed in rats with cardiac I/R injury as indicated by decreased %LVEF. In the brain, we found brain apoptosis, brain inflammation, microglia hyperactivation, and reactive astrogliosis occurred following cardiac I/R injury. Pretreatment with Z-VAD effectively increased %LVEF, reduced brain apoptosis, attenuated brain inflammation by decreasing IL-1β mRNA levels, suppressed microglial and astrocytic hyperactivation and proliferation after cardiac I/R injury. Conclusion: Z-VAD exerts neuroprotective effects against cardiac I/R injury not only targeting apoptosis but also microglial and astrocyte activation.