MK-801 reduced cerebral ischemic injury by inducing hypothermia

Brain Res. 1990 Apr 30;514(2):300-4. doi: 10.1016/0006-8993(90)91424-f.

Abstract

The non-competitive N-methyl-D-aspartate (NMDA) antagonist, MK-801, has been reported to prevent or attenuate ischemic brain damage in various animal models. In halothane-anesthetized gerbils it was found that an optimal dose of MK-801 (3.0 mg/kg) for providing cerebral protection also produced hypothermia (31.1 +/- 0.62 degrees C) relative to control animals (34.2 +/- 0.77 degrees C, P less than 0.01). This degree of hypothermia alone was sufficient to provide complete histological and functional protection (spatial memory) against 5 min of carotid artery occlusion. In gerbils made ischemic, but maintained at normal body temperature, a dose of 3.0 mg/kg of MK-801 provided no protection against hippocampal cell loss or spatial memory impairment. These data suggest that the protective actions of MK-801 may be due entirely to drug-induced hypothermia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Body Temperature Regulation / drug effects*
  • Dibenzocycloheptenes / pharmacology*
  • Dizocilpine Maleate
  • Female
  • Gerbillinae
  • Hypothermia / chemically induced
  • Hypothermia / physiopathology*
  • Ischemic Attack, Transient / drug therapy*
  • Ischemic Attack, Transient / pathology
  • Ischemic Attack, Transient / physiopathology
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter / antagonists & inhibitors
  • Receptors, Neurotransmitter / physiology*

Substances

  • Dibenzocycloheptenes
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Neurotransmitter
  • Dizocilpine Maleate