Protective effects of memantine against ischemia-reperfusion injury in Spontaneously Hypertensive Rats

Memantine, an uncompetitive NMDA open-channel blocker, has been shown to be effective in preventing neuronal damage after permanent focal cerebral isc hemia. Reperfusion after a long period of ischemia may aggravate the progre ssion of neuronal damage. Those drugs that show protective effects after pe rmanent cerebral ischemia, therefore, might fail to do so against ischemia- reperfusion injury. In this study we evaluated the effects of memantine on brain edema formation and ischemic injury Volume after transient cerebral i schemia. Male Spontaneously Hypertensive Rats (SHR) weighing 250-300 g were anesthetized with halothane and subjected to 1 hour of temporary middle ce rebral artery occlusion by an intraluminal suture. 20 mg/kg of memantine or saline were injected intraperitoneally 5 min. after the induction of ische mia. Physiological parameters and regional cerebral blood flow were monitor ed during the surgical procedure. Brain water content and ischemic injury v olume were measured with the wet dry method and 2,3,5-triphenyl tetrazolium chloride monohydrate (TTC) staining, respectively, at 24 hours after occlu sion. There were no statistically significant differences between the group s regarding physiological parameters during the procedure. Memantine treatm ent (n = 9) reduced the brain water content significantly in the cortex com pared to saline treatment (n = 8; 83.1 +/- 0.7% vs. 84.5 +/- 1.5%, respecti vely, p < 0.05). The total Volume of ischemic brain injury was 300 +/- 49 m m(3) in the animals treated with saline (n = 13). Treatment with 20 mg/kg m emantine (n = 14) reduced the ischemic injury volume to 233 +/- 61 mm(3) (P < 0.01). These results demonstrate that the harmful effects of recirculati on after a period of ischemia can be attenuated by the treatment of memanti ne, perhaps by its action at the NMDA receptors.