Methionine sulfoximine reduces cortical infarct size in rats after middle cerebral artery occlusion

Raymond A. Swanson, Kazuya Shiraishi, Matthew T. Morton, Frank R Sharp

Research output: Contribution to journalArticle

52 Scopus citations

Abstract

The methionine analogue methionine sulfoximine was administered to 10 rats 24 hours before occlusion of the proximal left middle cerebral artery. Three days later the rats were decapitated and the brain infarct volumes were compared with those in 10 control rats that received saline before middle cerebral artery occlusion. The mean volume of the infarct in the cerebral cortex was reduced by 33% in the group treated with methionine sulfoximine (p<0.01). This protective effect may be mediated by a presynaptic mechanism; methionine sulfoximine profoundly inhibits brain glutamine synthetase, thereby interrupting the astrocyte-neuron glutamate shuttle and impairing neuronal glutamate release. Methionine sulfoximine also increases brain glycogen stores, and this increased energy reserve may benefit penumbral tissue during the peri-infarct period. Further study of the mechanisms by which methionine sulfoximine decreases infarct volume could lead to new therapeutic approaches for stroke.

Original languageEnglish (US)
Pages (from-to)322-327
Number of pages6
JournalStroke
Volume21
Issue number2
StatePublished - Feb 1990
Externally publishedYes

Keywords

  • Cerebral ischemia
  • Glutamates
  • Methionine sulfoximine
  • Rats

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

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