PROLONGATION AND ENHANCEMENT OF POSTISCHEMIC C-FOS EXPRESSION AFTER FASTING

Background and Purpose A rapid but transient expression of c-fos after cerebral ischemia has been extensively documented. However, the mecha nism of this induction and whether induction of c-fos is neuroprotecti ve or detrimental to the brain after ischemia is presently nor clear. Fasting before transient cerebral ischemia has been shown to reduce de layed neuronal necrosis and infarct volume. The purpose of the present study was to examine the effect of preischemic fasting for 24 hours o n the expression of c-fos after transient focal cerebral ischemia. Met hods Focal cerebral ischemia was induced by temporary occlusion of the right middle cerebral artery and both com mon carotid arteries for 60 minutes. Male Long-Evans rats weighing 250 to 300 g were randomly div ided into two groups: fed (control group) and food deprived for 24 hou rs (fasted group) before ischemic surgery. Infarct volumes were measur ed on the basis of triphenyltetrazolium chloride-delineated infarct ar eas, and plasma glucose levels were determined by the glucose oxidase method. Temporal and spatial expression of c-fos was assessed by North ern blot analysis, in situ hybridization, and immunohistochemistry. Re sults Fasting for 24 hours before 60 minutes of ischemia resulted in a 26.6% decrease in preischemic plasma glucose levels and a 74.5% reduc tion in infarct volumes in the fasted group compared with the control group. A rapid but transient induction of c-fos mRNA was observed in t he ischemic cortex in control animals after 60 minutes of ischemia. Fa sting not only prolonged but also enhanced the intensity of c-fos expr ession in the ischemic cortex. Regional c-fos expression was also diff erent between these two groups. Conclusions The results support the co ntention that c-fos expression may be compatible with its purported ne uroprotective role in selected experimental paradigms. The signaling m echanisms underlying the effect of fasting and subsequent lowering of plasma glucose levels on postischemic c-fos expression remain to be ex plored.