Short therapeutic window for MK-801 in transient focal cerebral ischemia in normotensive rats

J Cereb Blood Flow Metab. 1996 Jan;16(1):107-13. doi: 10.1097/00004647-199601000-00013.

Abstract

The present study investigates the role of N-methyl-D-aspartate (NMDA) receptors in a model of transient focal cerebral ischemia in normotensive rats. The left middle cerebral artery and both common carotid arteries were occluded for 60 min. Preliminary studies indicated that this gave reproducible infarctions of the cortex and striatum. These infarctions were the result of severe ischemia followed by complete reperfusion after clamp removal, as showed by striatal tissue Po2 monitoring. Microdialysis indicated that glutamate concentration increased immediately after occlusion and returned to the baseline value 40 min after clamp removal. MK-801 (1 mg kg-1 i.v.), an antagonist of the NMDA glutamatergic receptor, reduced the cortical infarct volume by 29% (p < 0.001) and the striatal infarct volume by 14% (p < 0.05) when given just prior to ischemia, but had no neuroprotective activity when given 30 min after the onset of ischemia. This short therapeutic window for MK-801 suggests that NMDA receptors play only a transient role in reversible focal ischemia in rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analysis of Variance
  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Infarction / prevention & control
  • Corpus Striatum / drug effects
  • Disease Models, Animal
  • Dizocilpine Maleate / pharmacology*
  • Dizocilpine Maleate / therapeutic use
  • Glutamic Acid / analysis
  • Ischemic Attack, Transient / drug therapy
  • Ischemic Attack, Transient / physiopathology*
  • Male
  • Microdialysis
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate / drug effects*
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Reperfusion

Substances

  • Receptors, N-Methyl-D-Aspartate
  • Glutamic Acid
  • Dizocilpine Maleate