Effects of alpha-Lipoic Acid on Apoptotic Cell Death in Rat Hippocampus Following Transient Forebrain Ischemia-reperfusion Injury

ABSTRACT

PURPOSE: The purpose of this study was to evaluate effect of alpha-lipoic acid on apoptotic cell death in rat hippocampal neuron following transient forebrain ischemia-reperfusion (I/R) injury. METHODS: The four-vessel occlusion method was used to induce transient I/R injury in the forebrain of Sprague-Dawley rats. In the treatment group, alpha-Lipoic acid (LA) was administered subcutaneously at 50 mg/kg/day for 7 days before induction of I/R injury. RESULTS: Pretreatment with LA significantly reduced the number of TUNEL-positive neurons in the pyramidal cells layer of the hipocampal CA1 region 5 days after the ischemia, suggesting a marked reduction of apoptotic cell death. Pretreatment with LA also resulted in marked suppression at the transcript level of mRNA for caspase-3 at 24 hours, and decreased concentration of the active form of caspase-3 protein in the hippocampus at 1, 3, and 5 days after I/R injury. Furthermore, as indicated by western blot analysis, the concentration of apoptosis-inducing factor (AIF) in the hippocampus was reduced at 1 and 3 days after a transient I/R injury by pretreatment with LA. CONCLUSION: The results of this study suggest that LA has the potential to prevent neuronal cell death in the hippocampus by inhibiting intracellular signaling pathways responsible for apoptosis following transient I/R injury.