Differential regulation of cyclooxygenase-2 in the rat hippocampus after cerebral ischemia and ischemic tolerance

We investigated the temporal changes and cellular localization of cyclooxygenase-2 (COX-2) in the rat hippocampus during the induction of acquired ischemic tolerance by sublethal ischemia, and compared these changes with those occurring following transient forebrain ischemia. Adult male Sprague Dawley rats were subjected to either 10 min of lethal global ischemia with or without 3 min of sublethal ischemic preconditioning, or 3 min of ischemia only. A short (3 min) cerebral ischemia as well as lethal ischemia with preconditioning substantially and significantly upregulated COX-2 expression in dentate granule cells, as confirmed by immunoblot analysis. This became evident by 4 h, peaked at 1-3 days, and returned to the basal level around 7 days. COX-2 expression was also increased in CA2 and CA3 neurons, although with weaker staining intensity, but in CA1 neurons very weak immunoreactivity was transiently observed. In the ischemic hippocampus, however, in agreement with previous reports, COX-2 expression was induced strongly in vulnerable CA1 and hilar neurons as well as in resistant CA3 and dentate granule cells. These data demonstrated that COX-2 expression is upregulated in neuronal subpopulations destined to survive, i.e., in CA3 and dentate granule cells after ischemia and ischemia-tolerance induction, as well as in ischemia-vulnerable neurons, i.e., in CA1 neurons after lethal ischemia, suggesting that hippocampal neuronal subpopulations have differential sensitivity to COX-2 upregulation.