Molecular correlates of delayed neuronal death following transient forebrain ischemia in the rat

Following transient forebrain ischemia selective and delayed neuronal degeneration occurs in the CA1 sector of the hippocampus. It is presently unclear whether this cell death is related to programmed cell death (PCD), which occurs in neurons during development of the CNS. Recently, the expression of various genes, such as c-fos, c-jun mkp-1, cyclin D1, and hsp70 was found to be associated with PCD in model systems. We and others have described that these genes are also upregulated in the hippocampus following ischemia. Most notably, c-fos, c-jun, and hsp70 are expressed specifically in CA1 neurons at survival times shortly preceding cell degeneration in rat models of global ischemia. In addition, the gene products could be detected by immunohistochemical methods, despite a general impairment of protein synthesis. These finding are especially relevant, since recent report suggests a functional role for Fos family proteins and c-jun in PCD in neurons of the superior cervical ganglion. These results could be indicative for the occurrence of a PCD-related program in CA1 neurons ad corroborate several other lines of evidences, such as occurrence of DNA fragmentation. Clearly, further studies are necessary to elucidate the functional role of the gene inductions following ischemia in vivo.