Expression of the Apoptosis‐Effector Gene, Bax, Is Up‐Regulated in Vulnerable Hippocampal CA1 Neurons Following Global Ischemia

Abstract

The observation that delayed death of CAl neurons after global ischemia is inhibited by protein synthesis inhibitors suggests that the delayed death of these neurons is an active process that requires new gene expression. Delayed death in CAl has some of the characteristics of apoptotic death; however, candidate proapoptotic proteins have not been identified in the CAl after ischemia. We studied the expression of Bax protein and mRNA, a member of the bcl-2 family that is an effector of apoptotic cell death, after global ischemia in the fourvessel global ischemia model in the rat and compared these results with the expression of the antiapoptotic gene bcl-2. Bax mRNA and protein are both expressed in CAl before delayed death, whereas bcl-2 protein is not expressed. Bcl-2 protein expression, but not that of Bax, is increased in CA3, a region that is ischemic but less susceptible to ischemic injury. In the dentate gyrus, both Bax and bcl-2 proteins are expressed. The selective expression of Bax in CAl supports the hypothesis that Bax could contribute to delayed neuronal death in these vulnerable neurons by an independent mechanism or by forming heterodimers with gene family members other than bcl-2. Key Words: Apoptosis-Global ischemiabcl-2-Bax.

Autologous transplantation of adipose-derived mesenchymal stem cells attenuates cerebral ischemia and reperfusion injury through suppressing apoptosis and inducible nitric oxide synthase

“…In vitro studies have demonstrated that hypoxia in the brain following focal and global ischemia can trigger programmed cell death (26,27). Herein, a significant number of TUNEL-positive cells were observed in the ischemic regions in rats with MCAO for 2 h followed by reperfusion for 24 h. Caspase-3 is well-known as an executioner of apoptosis, and there is a significant body of evidence that activation of caspase-3 is observed after ischemic injury.…”

Different Expression Patterns of Bcl-2, Bcl-xl, and Bax Proteins After Sublethal Forebrain Ischemia in C57Black/Crj6 Mouse Striatum

“…The attenuation of lethal ischemia-induced DNA fragmentation by a conditioning ischemia-induced Bcl-2 and Bcl-xl overexpression indicates that Bcl-2 family proteins may take part in protective ischemic preconditioning induced by sublethal forebrain ischemia. In many experimental paradigms, level changes in the Bcl-2 family genes have been reported as early as 6 to 8 hours in hippocampus after lethal ischemia, [17][18][19] but the increased Bcl-2, Bcl-xl, and Bax mRNA levels were not consistent with protein levels, probably because of the decreased protein synthesis due to lethal ischemia. 20,21 In our experiment the Bcl-2 family mRNA level changes are observed to be consistent with those of the proteins.…”

Molecular Physiology of Preconditioning-Induced Brain Tolerance to Ischemia

“…In contrast, at the periphery of the ischemic core with focal insults, or in selectively vulnerable regions such as the hippocampus CA1 after a short period of ischemia, neurons may die over a longer period with morphological signs and biological features indicative of apoptosis (67,112). In this section, emphasis is placed on the welldocumented notion that an effective suppression of apoptosis is associated with brain tolerance.…”