Cerebroprotective properties of SM-20220, a potent Na+/H+ exchange inhibitor, in transient cerebral ischemia in rats

The aim of this study was to investigate the contribution of the Na+/H+ exchanger to cerebral ischemia using SM-20220 (N-(aminoiminomethyl)-1-methyl-1H-indole-2-carboxamide methanesulfonate), a newly synthesized compound. In in vitro experiments, we evaluated the inhibitory effect of SM-20220 on the Na+/H+ exchanger in cultured neurons and glial cells. The IC50 of SM-20220 in neurons and glial cells was 5 nM and 20 nM, respectively. To examine the in vivo effects of SM-20220 on brain injury, we used a transient middle cerebral artery occlusion model in rats. SM-20220 given intravenously 1 h after occlusion significantly reduced the extent of cerebral edema, Na+ content and infarcted area in a dose-dependent manner. The results of the present study suggest that the Na+/H+ exchanger is involved in the aggravation of brain edema and infarction, and its inhibitor may exert protective effects on post-ischemic brain damage. (C) 1999 Elsevier Science B.V. All rights reserved.