Rat B-2 sequences are induced in the hippocampal CA1 region after transient global cerebral ischemia

Global brain ischemia causes cell death in the CA1 region of the hippocampu s 3-5 days after reperfusion. The biological pathway leading to such delaye d neuronal damage has not been established. By using differential display a nalysis, we examined expression levels of poly(A) RNAs isolated from hippoc ampal extracts prepared from rats exposed to global ischemia and found an u p-regulated transcript, clone 17a, Northern blot analysis of clone 17a show ed an approximately 35-fold increase in the ischemic brain at 24 h after fo ur-vessel occlusion. Rapid amplification of cDNA ends of clone 17a revealed a family of genes (160-540 base pairs) that had the characteristics of rod ent B-2 sequences. In situ hybridization demonstrated that the elevated exp ression of this gene was localized predominantly in the CA1 pyramidal neuro ns. The level of expression in the CAI region decreased dramatically betwee n 24 and 72 h after ischemia, The elevated expression of done 17a was not o bserved in four-vessel occlusion rats treated with the compound LY231617, a n antioxidant known to exert neuroprotection in rats subjected to global is chemia, Since delayed neuronal death has the characteristics of apoptosis, we speculate that clone 17a may be involved in apoptosis, We examined the e xpression level of clone 17a in in vitro models of apoptosis using cerebell ar granule neurons that were subjected to potassium removal, glutamate toxi city, or 6-hydroxydopamine treatment and found that clone 17a transcripts w ere induced in cerebellar granule neurons by glutamate or B-hydroxydopamine stimulation but not potassium withdrawal.