Failure of ischemic neuroprotection by potentiators of gamma-aminobutyric acid.

Ken Madden, Wayne Clark, Nicola Lessov

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

INTRODUCTION: Potentiators of inhibitory neurotransmission may provide a neuroprotective effect on cerebral tissue exposed to ischemia, without inducing toxic side effects. Topiramate and vigabatrin enhance the action of gamma-aminobutyric acid (GABA), and each has side effect profiles known to be well tolerated through their clinical use as anticonvulsant medications. We assessed the potential benefit through GABA activation by these drugs on infarct size and functional recovery following focal cerebral ischemia in mice. METHODS: Silicon-coated suture was advanced through the internal carotid artery of 89 halothane-anesthetized mice to temporarily occlude the right middle cerebral artery for either 45 minutes (topiramate), or 120 minutes (vigabatrin). Animals were treated either at the time of reperfusion with topiramate (100 mg/kg, 40 mg/kg, or saline control), or two hours before arterial occlusion with vigabatrin, (1000 mg/kg, 500 mg/kg, or saline control). Neurological outcome was measured 24 hours after ischemia using a 28-point functional examination score. Infarct volume was estimated by summing area maps of stained slices of infarcted hemispheres. RESULTS: Functional examination scores at 24 hours were similar between the high dose topiramate group, the low dose topiramate group, and the control group. Similarly, no differences were noted between examination scores of high dose vigabatrin, low dose vigabatrin, and control. Consistent sized right hemisphere infarcts were noted within each group on histological examination. Mean infarct volumes did not differ between groups treated with high dose topiramate, low dose topiramate, or control. Infarct volumes of animals treated with saline control were slightly larger than that of high dose vigabatrin and low dose vigabatrin groups, but the difference did not reach significance. CONCLUSION: Treatment with these two potentiators of GABA did not result in significant differences in outcome following focal cerebral ischemia, by either functional or histological measures. These results do not support a substantial neuroprotective role of GABA following ischemia in this mouse suture model.

Original languageEnglish (US)
Pages (from-to)119-124
Number of pages6
JournalClin Med Res
Volume1
Issue number2
Publication statusPublished - Apr 2003
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)
  • Community and Home Care

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