Ischemia-induced inhibition of the initiation factor 2alpha phosphatase activity in the rat brain.

Rats were subjected to the standard four-vessel occlusion model of brain transient ischemia for 30 min. Following different recirculation periods, the level of phosphorylation of the initiation factor 2 subunit alpha (eIF2alpha) and the eIF2alpha kinase/s and phosphatase/s activity were determined. eIF2alpha phosphorylation significantly increased very early during reperfusion (10-30 min), recovering at 4 h of reperfusion. Activation of any eIF2alpha kinases studied during ischemia or reperfusion was not noted. Conversely, eIF2alpha phosphatase activity significantly decreased at 10-15 min of reperfusion, reaching values even higher than in controls at 2-4 h of reperfusion. Our results support the hypothesis that the reperfusion-induced phosphorylated eIF2alpha changes are at least a result of the transiently eIF2alpha phosphatase inhibition.