Cooperative expression of survival p-ERK and p-Akt signals in rat brain neurons after transient MCAO.

In order to determine possible coordinate expression of major survival signals, immunofluorescent analyses for phosphorylated ERK (p-ERK) and phosphorylated Akt (p-Akt) were carried out after 90 min of transient middle cerebral artery occlusion (MCAO) in rats. p-Akt single positive cells (E-/A+) were found in the sham control brains with weak signal intensity. The levels of both survival signals concurrently increased from 1 to 3 h after the reperfusion with the peak at 1 h, and the signals were much stronger in the ischemic penumbra (IP) than ischemic core (IC). The number of E-/A+ cells was larger in both the IC and IP than that of p-ERK single positive cells (E+/A-). The E+/A- cells were primarily expressed at 1 h in the IP. The number of p-ERK plus p-Akt double positive cells (E+/A+) peaked at 1 h, and the intensity was much stronger in the IP than IC. These findings suggest that p-ERK and p-Akt play independent roles, respectively as emergency or maintenance signal for survival at an early stage after reperfusion, and that both signals were cooperatively expressed especially in the IP.