Expression of immediate-early gene proteins in the rat hippocampus following transient global ischemia.

The temporospatial expression patterns of the immediate-early gene (IEG) proteins Fos, FosB, $\Delta$FosB, Jun, JunB, JunD, and NGFI-A were investigated in rat hippocampus by immunonohistochemistry 2 h, 12 h, 24 h, and 48 h after forebrain ischemia. Transient global ischemia (20 min), produced by four vessel occlusion (4-VO), elicited different patterns of IEG expression in vulnerable CA1 and more resilient CA3 neurons. Cell counts revealed that initially, ischemia elevated immunoreactivity in both CA1 and CA3 hippocampal subfields for all IEGs examined, with the exception of JunD and NGFI-A. However, distinct patterns of IEG expression became evident in these regions at later time points following recirculation of blood flow. The pivotal difference was the persistence of ischemia-induced elevations of FosB and Jun expression in the CA1 region of the hippocampus. Unlike CA3 neurons where IEG immunoreactivity had subsided to basal levels by 24 h-48 h after reperfusion, CA1 neurons continued to display increased FosB- and Jun-like immunoreactivity 48 h post-ischemia. In contrast to FosB and Jun, JunB expression declined significantly below basal levels in CA1 neurons at 48 h, while JunB-like immunoreactivity remained unaltered in CA3 neurons. Given that JunB has been shown to inhibit the transactivating properties of Jun, decreased JunB levels may contribute to the apoptotic death of CA1 neurons by enhancing the transcriptional regulating activity of Jun. Also notable at 48 h was the complete loss of constitutive NGFI-A expression from CA1 neurons of ischemic animals. In summary, these findings suggest that persistent elevations in FosB and Jun expression coupled with reductions in JunB and NGFI-A levels may play a role in the apoptotic death of CA1 neurons following transient global ischemia. (Abstract shortened by UMI.