EXPRESSION OF NGFI-B MESSENGER-RNA IN A RAT FOCAL CEREBRAL ISCHEMIA-REPERFUSION MODEL

Cerebral ischemia is known to induce the expression of several immedia te early genes (IEGs), including c-fos and c-jun, which subsequently r egulate a number of late effector genes. In this study, we examined th e expression of NGFI-B (or nur77) mRNA in a rat focal cerebral ischemi a-reperfusion model. NGFL-B is a member of the IEGs which encodes for a nuclear receptor and is rapidly induced by nerve growth factor (NGF) . Northern blot analysis showed a rapid but transient enhancement of N GFI-B mRNA, a peak level for which was observed at 30 min of reperfusi on following 60 min ischemic insult. At the peak level, quantitative a nalysis of the blot indicated a 12-fold and 4-fold increase of NGFI-B mRNA in the ischemic cortex and ipsilateral hippocampus, respectively, as compared to the sham-operated control. No apparent changes in mRNA levels were observed within contralateral sites of the cortex. Result s from in situ hybridization showed that severe ischemia (60 min) resu lted in a marked increase of NGFI-B mRNA throughout the entire ischemi c cerebral cortex. The increase was particularly notable in the fronta l, occipital, perirhinal and piriform cortical regions and in the dent ate gyrus and CA1-3 regions of the ipsilateral hippocampus. A marked i nduction was also noted in the ipsilateral caudate putamen. Unlike the induction profile of NGFI-B mRNA, severe ischemia resulted in bilater al increases of its family gene, NGFI-A mRNA. The spatial induction pr ofile is similar to that of NGFI-B mRNA in both hemispheres, except wi thin the region of the contralateral dentate gyrus which showed low le vels of NGFI-A mRNA. The expression pattern of NGF and BDNF mRNA, upst ream genes of NGFI-B, were also examined. Interestingly, the temporal and spatial expression patterns of BDNF mRNA were very similar to that of NGFI-A mRNA under the same conditions, whereas increased NGF and N GFI-B mRNA were observed only in the ipsilateral hemisphere. It is lik ely that multiple and/or overlapping pathways are activated subsequent to ischemic challenge which in turn are crucial for cell survival and /or functional recovery following focal cerebral ischemia.