The effects of propofol on hippocampal caspase-3 and Bcl-2 expression following forebrain ischemia–reperfusion in rats

Abstract

Transient cerebral ischemia may result in neuronal apoptosis. During this process, several apoptosis-regulatory genes are induced in apoptotic cells. Among these genes, cysteinyl aspartate-specific protease-3 (caspase-3) and B-cell leukemia-2 (Bcl-2) are the most effective apoptotic regulators because they play a decisive role in the occurrence of apoptosis. Research has shown that propofol, which is an intravenous anesthetic agent, exhibits neuroprotective effects against cerebral ischemia–reperfusion injury, although the neuroprotective mechanism is still unclear. In this study, we examined the effects of propofol in rats after forebrain ischemia–reperfusion. We assessed the expression of hippocampal caspase-3, which acts as an apoptotic activator, and Bcl-2, which acts as an apoptotic suppressor. Forebrain ischemia was induced in hypotensive rats by clamping the bilateral common carotid arteries for 10 min. Propofol was administered via a lateral cerebral ventricle injection using a microsyringe after the induction of ischemia. Neuronal damage was determined by histological examination of brain sections at the level of the dorsal hippocampus. Caspase-3 and Bcl-2 expression in the hippocampus were detected using semiquantitative reverse transcription–polymerase chain reaction (RT–PCR) and Western blot analysis. We also used an immunohistochemical method after ischemia–reperfusion. In the hippocampus, caspase-3 and Bcl-2 mRNA were dramatically increased at 24 h after forebrain ischemia. Following 6–24 h of reperfusion, forebrain ischemia for 10 min induced a gradual increase in the expression of caspase-3 and Bcl-2 protein in the rat hippocampus, which peaked at 24 h. In the propofol (1.0 mg/kg) intervention group, the hippocampal expression of caspase-3 mRNA decreased significantly in rats 24 h after ischemia; Bcl-2 mRNA was increased at the same time point. During the 24-h reperfusion period and after treatment with propofol, the level of caspase-3 protein expression was low, while the level of Bcl-2 was high. Thus, our results suggest that the neuroprotective effects of propofol against neuronal apoptosis may be mediated by the inhibition of caspase-3 expression and an increase in Bcl-2 expression.