Focal cerebral ischemia causes two temporal waves of Akt activation

Abstract
We studied whether pro-survival Akt was activated after transient focal cerebral ischemia and whether it inhibited pro-apoptotic Bad. Phosphorylation of Akt (serine-473) was enhanced in cortex after 1-hour ischemia, and also after 1h and 6 h of reperfusion, but it returned back to that in controls by 24 h. After this first wave of Akt activation, a second increase was observed between 4 and 7 days. In striatum, only the late Akt activation was seen. In contrast to Akt, no Bad phosphor ylation (serine-136) was detected after ischemia. Therefore, injury spontaneously activated Akt, but this did not suppress Bad signalling. It is proposed that further pharmacological activation of Akt shortly after ischemia might promote cell survival, whereas Akt activation at longer time points is involved with glial reactivity.