SM-20220, a Na+/H+ exchanger inhibitor: Effects on ischemic brain damage through edema and neutrophil accumulation in a rat middle cerebral artery occlusion model

Yasuhiro Suzuki, Yuji Matsumoto, Yasuhiko Ikeda, Kazunao Kondo, Naohito Ohashi, Kazuo Umemura

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

The Na+/H+ exchanger (NHE) is activated during ischemia-reperfusion in an effort to restore intracellular pH to normal levels. The NHE is recognized to exist as a distinct protein in the plasma membranes of a variety of cells. We investigated the pharmacological effects of a Na+/H+ exchanger inhibitor, SM-20220 (N-(aminoiminomethyl)-1-methyl-1-H-indole-2-carboxamide methanesulfonate), on ischemic brain damage, edema and neutrophil accumulation at 72 h after middle cerebral artery (MCA) occlusion in a rat MCA occlusion model. SM-20220 was intravenously administered as a bolus injection immediately after occlusion, followed by a continuous infusion over 2.5 h. At 72 h after occlusion, the infract area was measured using hematoxylin-eosin staining and, using the same slices, neutrophils in the brain were immuno-stained with anti-myeloperoxidase (n=11). In a separate study, rat behavior was scored and scaled, and brains removed for the determination of water content by the dry-weight method. SM-20220 significantly (P<0.05) attenuated cerebral infarct volume, water content, and the neutrophil accumulation at 72 h after the MCA occlusion, and ameliorated neurological deficits. SM-20220, an NHE inhibitor prevented the progress of cerebral ischemic damage and edema following MCA occlusion in rats though a possible mechanism that may be due to the inhibition of neutrophil accumulation. The NHE in neutrophils may enhance the progress of cerebral damage following cerebral ischemia-reperfusion.

Original languageEnglish
Pages (from-to)242-248
Number of pages7
JournalBrain Research
Volume945
Issue number2
DOIs
Publication statusPublished - 02-08-2002

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Fingerprint Dive into the research topics of 'SM-20220, a Na<sup>+</sup>/H<sup>+</sup> exchanger inhibitor: Effects on ischemic brain damage through edema and neutrophil accumulation in a rat middle cerebral artery occlusion model'. Together they form a unique fingerprint.

Cite this