Immunohistochemical analysis of cyclic AMP response element binding protein phosphorylation in focal cerebral ischemia in rats.

Phosphorylation of cyclic AMP response element binding protein (CREB) is one of the most important mechanisms controlling various gene transcriptions. In the present study, the phosphorylation of CREB was examined immunohistochemically at 24 h of recirculation following 1.5 h of middle cerebral artery occlusion (MCAO) in rats. MCAO was induced by the intraluminal suture method. The infarct core revealed a significant reduction in the number of immunoreactive cells with the anti-phosphorylated CREB and with the anti-CREB antibody, which binds to both unphosphorylated and phosphorylated CREB. In contrast, the peri-infarct area exhibited a marked increase in the number of immunopositive cells as well as in the intensity of nuclear staining with each antibody, so that almost all of the cells expressing CREB demonstrated phosphorylation of CREB. On the other hand, about half of the CREB immunopositive cells reacted weakly with the anti-phosphorylated CREB antibody in the sham group. These findings indicated that the expression as well as phosphorylation of CREB protein was significantly activated in the regions surrounding the infarct area. Since phosphorylation of CREB has recently been implicated in signal transductions that promote the survival and differentiation of neurons, the present data suggest that tissue repair mechanisms may be markedly activated in the peri-infarct area. Copyright 1999 Elsevier Science B.V.