EXPRESSION OF ZINC-FINGER IMMEDIATE-EARLY GENES IN RAT-BRAIN AFTER PERMANENT MIDDLE CEREBRAL-ARTERY OCCLUSION

The prolonged expression of the leucine zipper fos/jun immediate early genes (IEG) has been correlated with neuronal death after cerebral is chemia. In this study, the expression of six zinc finger LEG was exami ned using in situ hybridization in adult rats after middle cerebral ar tery occlusion (MCAO) with the suture model. NGFI-A, NGFI-B, NGFI-C, e gr-2, egr-3, and Nurr1 mRNA were all induced throughout the ipsilatera l cortex at 1 hour to 12 hours after MCAO. The cortical induction for most of the genes was greatest in the anterior cingulate and the anter ior cerebral artery (ACA) and middle cerebral artery (MCA) transition zone. All of the zinc finger IEG were induced at 1 hour in all regions of hippocampus. NGFI-A and NGFI-B were induced in ipsilateral thalamu s. Within areas of infarction, the basal LEG mRNA expression, and expr ession of the housekeeping gene cyclophilin A mRNA, decreased below co ntrol levels by 12 hours after the ischemia. Immediate early gene expr ession outside areas of infarction returned to control levels in most brain regions by 24 hours except for egr-3, which continued to be indu ced in the MCA/ACA transition zone for 24 hours, and NGFI-A, which con tinued to be expressed in specific regions of the thalamus for 72 hour s. The induction of these IEG in the cortex is likely caused by ischem ia-induced cortical spreading depression, with the hippocampal and tha lamic LEG induction being caused by activation of efferent cortical pa thways to these regions. The prominent induction of NGFI-B, NGFI-C, eg r-2, and egr-3 in the anterior cingulate cortex, the ACA/MCA transitio n zone, and medial striatum could reflect the ischemic regions around MCA infarcts. The prolonged NGFI-A expression observed in thalamus in this study, and in CAI of hippocampus after global ischemia in the ger bil in a previous study, suggests that the prolonged NGFI-A expression could be the result of or the cause of the delayed cell death. Prolon ged NGFI-A expression, like c-fos and c-jun, seems to provide a marker for slowly dying neurons.