Effect of Hypothermia on Ischemia-induced Apoptosis: Immunohistochemical Detection of Bax, Caspase-3 and Bcl-2 Proteins

Kim, Yong Jae

Abstract

BACKGROUND: Hypothermia has been demonstrated to prevent delayed neuronal death following transient ischemia. Although both apoptosis and necrosis have been shown to contribute to neuronal cell death, the ability of hypothermia to prevent apoptosis remains unknown.
METHODS
To test the hypothesis that hypothermia reduces neuronal injury in part by decreasing apoptosis, gerbils that underwent hypothermia and normothermia were subjected to 10 minutes of global ischemia. The patterns of expression of bax, caspase-3 and bcl-2 proteins were examined immunohistochemically in the hippocampal CA1 area of the gerbil brain at 1, 3 and 7 days after ischemia.
RESULTS
Following transient global ischemia, levels of Bax and caspase-3 proteins, identified as proapoptotic molecules, were increased in CA1 neurons. A decrease in immunoreactivity against Bax and caspase-3 in the hypothermic group as compared to normothermic group was correlated with the CA1 neuronal protection. Time course studies revealed that time dependent increases of these proapoptotic proteins, peaked at 3 days. The expression of antiapoptotic Bcl-2 oncoproteins was observed in CA1neurons 3 days after ischemia in the hypothermic group.
CONCLUSIONS
These results suggest that hypothermia reduces delayed neuronal death in part by decreasing apoptosis after transient global ischemia. Antiapoptotic bcl-2 protein may play a neuroprotective role in the setting of hypothermia. (J Korean Neurol Assoc 19(3):285~293, 2001)