Abstract
Cyclic AMP response element binding protein (CREB) is a transcription factor expressed constitutively primarily in neurons and is activated by phosphorylation at Ser^133^ residue. CREB mediates expression of several neuroprotective proteins, including B‐cell CLL/lymphoma 2 (BCL‐2) and brain‐derived neurotrophic factor (BDNF). Although phosphorylation of CREB after ischemia has been investigated extensively, CRE‐mediated gene transcription after ischemia is not as well studied. We investigated temporal changes in CRE‐mediated gene transcription in the cerebral cortex after focal ischemia in transgenic mice with a CRE‐lacZ reporter gene. In the ischemic core, X‐gal‐positive cells, which reflected expression of the CRE‐lacZ reporter gene, were observed rarely at any time point, though transient phosphorylation of CREB was detected. In contrast, the peri‐infarct area showed a persistent increase in the number of X‐gal‐positive cells, of which more than half were positive for neuronal nuclei (NeuN). Our results suggest that CRE‐mediated gene transcription, the pattern of which is not always consistent with that of CREB phosphorylation, occurs primarily in neurons in the peri‐infarct area after focal cerebral ischemia and may be a neuroprotective response against ischemic insult. © 2003 Wiley‐Liss, Inc.