Cerebral protection against ischemia by locomotor activity in gerbils. Underlying mechanisms

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.

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 D2, prostaglandin F2 alpha, and thromboxane B2 were measured in ventriculocisternal perfusate. In additional animals cerebral blood flow was assessed by hydrogen clearance.

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 D2, prostaglandin F2 alpha, and thromboxane B2. In nonrunners, however, thromboxane B2 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).

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.