THE ROLE OF THE CYCLIC AMP-RESPONSIVE ELEMENT-BINDING PROTEIN (CREB) IN HYPOXIC-ISCHEMIC BRAIN-DAMAGE AND REPAIR

The cyclic AMP-responsive element binding protein (CREB) is a basally expressed, post-translationally activated transcription factor that ha s been implicated in the trans-activation of a number of genes in resp onse to cAMP and calcium signals. A unilateral hypoxic-ischemic (HI) i njury in the 21 day old rat was used to examine a potential role for C REB (phosphorylated and unphosphorylated) in neuronal programmed cell death or cell survival. The selectively vulnerable CA1 pyramidal cells , which undergo delayed neuronal death following mild HI, show a loss of CREB and phosphorylated CREB (pCREB) immunoreactivity on the injure d side 48 and 72 h following HI. In contrast the resistant dentate gra nule cells and cortical cells produce a bimodal increase in pCREB immu noreactivity, peaking 6 and 48 h following HI. The fact that cells sur viving the HI insult are showing increased activation of CREB suggests that this protein might be involved in the process of neuroprotection .