Cyclic AMP Response Element Binding Protein Phosphorylation May Be Closely Associated with Neuroprotective Mechanisms After Focal Ischemia in Rat Brain

Summary

The phosphorylation of cyclic AMP response element binding protein (CREB) was immunohistochemically examined in the rat brain at 3.5 h, 12 h, 24 h, 48 h, 7 days and 14 days of recirculation after focal ischemia, which was 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, such as the frontoparietal somatosensory cortex, revealed a significant, but transient increase in the 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 areas such as the frontoparietal motor cortex and the hippocampus CA1, the number of phosphorylated CREB-positive cells showed a more marked increase compared with that in the ischemic core at 3.5 h of recirculation. This increase continued until 48 h of recirculation, with a tendency for gradual decline. Cresyl violet staining at 48 h and the subsequent time points revealed that almost complete neuronal loss with apparent activation of glial cells occurred in the ischemic core, whereas no apparent loss of neurons was noted in the per ischemia areas. 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.