Delayed induction of JunB precedes CA1 neuronal death after global ischemia in the gerbil

The immediate early genes (IEGs), c-jun, junB and c-fos are expressed after global ischemia in the gerbil. The role of these genes remains unclear. Wh ilst moderate ischemia (7 min) causes delayed CA1 neuronal death, pre-condi tioning with mild ischemia (2 min) neuroprotects the CA1 subfield. This dif ferential response allows the specific expression patterns of IEGs to be as sociated with either delayed neuronal death, or cell survival, depending up on the insult severity. Using a graded insult strategy we have shown that ( 1) early IEG expression is prominent in the neuronal layers of the CA3, hil ar and dentate regions, and (2) a delayed, secondary wave of JunB expressio n is localized to the selectively vulnerable CA1 neuronal layer after moder ate ischemia. This expression precedes the histological and histochemical f eatures of neuronal death. Delayed JunB expression was not observed in anim als subject to 2 min ischemia. The glial fibrillary acidic protein (GFAP) p romotor possesses an AP-1 binding site, the target for IEG dimers. To exami ne the possible link between IEG expression and astrocyte activation the tr anscriptional activation of GFAP was assessed. GFAP mRNA was evident within 8 h of ischemia after both insults. The extent of the astrocytic reaction was dependent upon the severity of the ischemia. The temporospatial distrib ution of IEG and GFAP expression differed, indicating that glial activation is unlikely to be regulated by the hippocampal expression of IEGs. We conc lude that early IEG expression is involved in signalling mechanisms that in voke neuroprotective effects in the dentate and CA3 regions, and that delay ed JunB expression in the CA1 subfield is associated with neuronal death, a nd may be involved in the commitment or execution phases of cell death. Ear ly astrocytic responses may play a role in the mechanism of ischaemic toler ance. (C) 1999 Elsevier Science B.V. All rights reserved.