EDEMA, CATION CONTENT, AND ATPASE ACTIVITY AFTER MIDDLE CEREBRAL-ARTERY OCCLUSION IN RATS

Background and Purpose: Reduction of cerebral blood flow results in several acute metabolic disturbances, including a reduction in Na,K-ATPase activity. The relation between this reduction and the onset of edema is unknown, as is the effect of restoration of blood flow. Therefore, we investigated the role Of decreased Na,K-ATPase activity in the pathogenesis and time course of ischemic brain edema and reperfusion. Methods: The middle cerebral arteries of rats were occluded by cannulation with a nylon suture for 30, 60, 120, or 240 minutes. The animals were then decapitated (permanent occlusion) or the suture was withdrawn to allow 24 hours of reperfusion before decapitation (temporary occlusion). Na,K-ATPase activity and Na+, K+ and water contents were measured at various intervals. Results: In the ischemic hemisphere, Na,K-ATPase activity was significantly decreased at 30, 60, 120, and 240 minutes of permanent occlusion (p<0.05). There was also a significant decrease in rats subjected to 60 or 120 minutes of temporary occlusion followed by 24 hours of reperfusion. Water content increased after 60, 120, or 240 minutes of permanent occlusion (p<0.01); after 24 hours of reperfusion, water content remained elevated (p<0.01). The Na+ content increased after both permanent and temporary occlusion, and the K+ content decreased only after permanent occlusion. Increases in water content correlated with decreases in Na,K-ATPase activity after temporary occlusion and with the Na+: K+ ratio after permanent occlusion. Conclusion: Reduction in Na,K-ATPase activity resulting in disruption of cellular ionic homeostasis may account for early development of cytotoxic brain edema after permanent occlusion of the middle cerebral artery. Such edema is also present 24 hours after 60 and 120 but not 30 minutes of temporary occlusion.