Temporal profile of CREB phosphorylation after focal ischemia in rat brain.

The phosphorylation of cAMP response element binding protein (CREB) in the rat brain was examined immunohistochemically at 3.5 h, 12 h, 24 h and 48 h of recirculation after focal ischemia induced by occlusion of the middle cerebral artery for 1.5 h. Brain sections were stained with affinity purified anti-phosphorylated CREB antibody. The ischemic core revealed a significant, but transient increase in number of phosphorylated CREB-positive cells at 3.5 h of recirculation, followed by a rapid decrease during the subsequent period. In the peri-ischemia area, the number of phosphorylated CREB-positive cells showed a more marked increase as compared to that in the ischemic core at 3.5 h of recirculation, and the increase continued until 48 h of recirculation with a tendency for gradual decline. Persistent enhancement of CREB phosphorylation may thus be closely related to the neuronal viability and neuroprotective mechanisms, whereas rapid disappearance of CREB phosphorylation may clearly precede neuronal death.