Neuronal apoptosis and apoptosis-related gene expression in the hippocampai CA1 region following cerebral ischemia in gerbils and their changes after intervention with mild hypothermia

Abstract

Objective To study the neuronal apoptosis and expressions of apoptosis-related genes in the hippocampal CAI region after cerebral ischemia in gerbils and investigate the protective effects of mild hypothermia. Methods Seventy-two gerbils were randomized equally into sham-operated group, hypothermic sham-operated group, normothermic ischemia-reperfusion (IR) group and hypothermic IR groups, and 5-minute forebrain iscbemia was induced in the latter 2 groups by bilateral common carotid artery obstruction. Normothermic or mild hypothermic condition was applied to the groups after the operation as indicated. At 1, 3 and 7 days after the operation, 6 gerbils were selected from each group for behavioral test using open field test, followed by detection of neuronal apoptosis in the hippocampal CAI region using TUNEL staining and by immunohistocheraistry for p53 and nuclear factor-kB (NF-kB) expressions. Results In normothermic condition, the 5-minute forebrain ischemia induced significant enhancement of the exploratory activities in the gerbils 1, 3 and 7 days after the operation (P<0.05). This enhancement was observed only 1 day after the operation in mild hypothennic condition (P<0.05). Increased neuronal apoptosis and up-regulated expressions of p53 protein and NF-kBin the hippocampal CA1 region occurred after the forebrain ischemia as shown by TUNEL staining and immunohistochemistry, and all these changes were significantly inhibited by the application of mild hypothermia (P<0.05). Conclusions Up-regulated p53 and NF-kB protein expression in the hippocampal CA1 region might be one of the mechanisms for ischemia-induced neuronal apoptosis in gerbils, and mild hypothermia may produce protective effects against these changes for brain protection following the iscbemia. Key words: Brain ischemia; Apoptosis; Mild hypothermia; p53 protein; Nuclear factor-kB