Expression of Immediate Early Genes Messenger RNAs in Focally Ischemic Rat Brain Following Delayed Postischemic Hyperthermia

Kim, Young; Ginsberg, Myron D

Abstract

Previous studies have indicated that hyperthermic modulation in the delayed postischemic period, even when occurring days after an ischemic insult, may augment ischemic injury. In order to evaluate the molecular mechanisms of the detrimental effects of hyperthermia on ischemic outcome, we performed a study to assess the effects of delayed postischemic hyperthermia on the regional expression of message for the immediate early genes c-fos and c-jun. 60 minutes of transient middle cerebral artery occlusion was produced in rats by insertion of an intraluminal filament. 24 hours after reperfusion, rats which were awake were subjected to normothermic(37-38degreesC) or hyperthermic(40degreesC) temperature modulation for 3 hours in a heating chamber. Either 2 or 24 hours after temperature modulation, brains were examined for mRNA expression of c-fos and c-jun by the dot blot method. Four regions of interest were chosen: fronto-cingulate, sensorimotor, piriform-insular cortex, and caudoputamen. Dot blot analysis revealed that c-fos mRNA at 2 hours after temperature modulation was significantly upregulated in the ipsilateral fronto-cingulate cortex-the site of the ischemic penumbra- in rats exposed to ischemia+delayed hyperthermia, in comparison to rats exposed to sham+normothermia(one-way ANOVA with post-hoc Bonferroni's test, p<0.05). In contrast, c-jun mRNA was significantly upregulated by ischemia+delayed hyperthermia within regions of core ischemia-i.e., sensorimotor and piriform-insular cortex, and caudoputamen. These findings have extended those of our earlier histopathological study10) to show that a significant increase in c-fos or c-jun expression may be closely linked to cellular survival or death after delayed moderate hyperthermia following ischemia.