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

J Korean Neurol Assoc > Volume 19(3); 2001 > Article

Journal of the Korean Neurological Association 2001;19(3): 285-293.

저체온이 허혈 고사에 미치는 효과:Bax,Caspase-3, Bcl-2 단백질의 면역화학적 발현

이화여자대학교 의과대학 신경과학교실

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

Yong-Jae Kim, M.D.

Department of Neurology, College of Medicine, Ewha Womans University

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 immunohistochemical-ly in the hippocampal CA1 area of the gerbil brain at 1, 3 and 7 days after ischemia. Results : Following transient glob-al 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 Key Words : Cerebral ischemia, Hypothermia, Apoptosis, Bax, Caspase-3, Bcl-2, and TUNEL