Apoptosis-Related Genes Are Expressed in the Rat Model of Subarachnoid Hemorrhage

Summary

Apoptosis in neurons can be induced by mild cerebral ischemia. We developed a rat model of subarachnoid hemorrhage that caused mild ischemic stress to the brain and detected expression of apoptosis-related genes in the hippocampus. Intracranial carotid bifurcation of the rat was perforated by a 3–0 nylon and subarachnoid hemorrhage induced. The intracranial pressure rose immediately to a level similar to systemic arterial pressure for 30 s to 1 min and returned to baseline by 20 min. We detected mRNA expression of bax, bcl-2, bcl-x, ice, p53 and p21 (Waf1) using an in situ hybridization technique. With this model, about one-third of the CA1 neurons were TUNEL-positive at 48 h after perforation, and histological findings were compatible with apoptotic cell changes. The bax, bcl-2, and bcl-x mRNA were expressed transiently at CAl pyramidal neurons, with a peak at 12 h. The bax tended to be expressed for a longer period than bcl-2. The CA3 pyramidal neurons showed bax, bcl-2, and bcl-x mRNA expression as well, but transiently and with an intensity that was about half that at CAl. The ice mRNA, the key enzyme for protease cascade, was upregulated at CA1 neurons with a peak at 12–18 h. The p53 mRNA expression was transient with maximum levels at 12 h, indicating that p53 is located upstream of bax expression. The p2l(Waf1) expression, however, reached maximum levels at 48 h and lasted until 120 h, suggesting no relation to bax or bcl-2 expression. The results may relate to delayed ischemic neurological deficit, which is often observed as a result of subarachnoid hemorrhage and vasospasm.