Coordinate expression of survival p-ERK and proapoptotic cytochrome c signals in rat brain neurons after transient MCAO.

In order to determine possible coordinate expression of major survival and proapoptotic signals, immunofluorescent analyses for phosphorylated ERK (p-ERK) and cytochrome c were carried out after 90 min of transient middle cerebral artery occlusion (MCAO) in rats. Strong induction of p-ERK was primarily expressed in the ischemic penumbra, while that of cytosolic cytochrome c signal was strongly induced in the ischemic core from 3 min to 3 h of reperfusion. The double-stained cells with strong p-ERK/weak cytochrome c became most apparent at 3 min primarily expressed in the ischemic penumbra, whereas the cells with weak p-ERK/strong cytochrome c were predominantly found in the ischemic core at 3 h. The proportion of double positive cells among the total number of single positive cells decreased in the ischemic core, and increased in the ischemic penumbra. These findings suggest that the coordinate expression of p-ERK and cytochrome c is fundamentally involved in cell survival or death at the early stage of reperfusion, and that they could play roles in different temporal and spatial profiles. Copyright 2002 Elsevier Science B.V.