The Effect of Duration of Ischemia and Body Temperature on the Expression of Bax/Bcl-2 in Transient Global Ischemia

ABSTRACT

BACKGROUND: Transient global ischemia causes delayed neuronal death (DND) in the CA1 area, of which the mecha-nism is controversial. Induction of apoptosis-regulating proteins during the process of DND has been reported, howev-er ,the exact role of Bcl-2/Bax is not well understood. We tried to reveal the pattern of the Bax/Bcl-2 expression modi-fied by the duration of ischemia and hypothermia. METHODS: Global ischemia was induced in Mongolian gerbils for 2, 5, and 10 minutes under the temperature of 36 degrees C and 32 degrees C. Hippocampal sections were evaluated 48 hours after ischemia with H&E and immunohistochemical staining to Bcl-2/Bax. Viable neuronal density and semi-quantitative grading were compared. RESULTS: In the CA1 area, neurons were intact in 2 min ischemia, while partial or significant ischemic changes were observed in 5-10 min ischemia of 36 degrees C setting, which were less severe in 32 degrees C . Bcl-2 was posi-tive in 2 min ischemia, while negative in 5~10 min ischemia of 36 degrees C . Bax was negative in 2 and 10 min ischemia, while positive in 5 min ischemia. In 32 degrees C setting, Bcl-2 was also positive in 2 min ischemia and partially positive in 5- 10 min ischemia, although Bax expression was not different from 36 degrees C. CONCLUSIONS: The complex mechanism of DND, which is in the spectrum of apoptosis and necrosis, seems to be determined by the severity of ischemia. The bal-ance between Bcl-2 and Bax may determine the survival of neurons in mild to moderate ischemia. Further evidence remains to be determined by morphological and molecular biological methods.