Cerebral Protection Against Ischemia by Locomotor Activity in Gerbils

Abstract

Background and Purpose A previous communication of this laboratory demonstrated reduced mortality and neuronal damage by spontaneous locomotor activity preceding forebrain ischemia in Mongolian gerbils. The present experiments seek to elucidate potential mechanisms of protection by measurement of cerebral blood flow, cerebral tissue conductance as an indicator of ischemic cell swelling, and the cerebral release of eicosanoids. Methods Gerbils were maintained either in conventional cages (nonrunners) or with free access to running wheels (runners) for 2 weeks preceding 15 minutes of forebrain ischemia. During ischemia and 2.5 hours of reperfusion, cerebral tissue conductance was determined with a two-electrode system. Simultaneously, prostaglandin D 2 , prostaglandin F 2α , and thromboxane B 2 were measured in ventriculocisternal perfusate. In additional animals cerebral blood flow was assessed by hydrogen clearance. Results Decreases in tissue conductance during ischemia were similar in nonrunners (56±3%) and runners (62±3%) but normalized more rapidly in runners during reperfusion. In both groups reperfusion was accompanied by marked increases of perfusate prostaglandin D 2 , prostaglandin F 2α , and thromboxane B 2 . In nonrunners, however, thromboxane B 2 was already elevated during ischemia (147±9%, P <.01) and remained elevated longer during recirculation ( P <.05). Postischemic perfusion maxima were higher in runners (70.8±7.4 versus 47.0±5.0 mL/100 g per minute, P <.05) and were observed sooner (27.4±6.9 versus 62.2±12.3 minutes, P <.05). Both groups displayed delayed hypoperfusion of a similar magnitude (runners, 29.0±2.4 mL/100 g per minute; nonrunners, 30.1±2.4 mL/100 g per minute). Conclusions Protection by preischemic locomotor activity may involve enhanced postischemic reperfusion, leading to more rapid normalization of conductance and thus of cell volume. Enhanced reperfusion may be the consequence of attenuated thromboxane liberation during and after ischemia.