MK-801 reduced cerebral ischemic injury by inducing hypothermia.
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.
Corbett
D
D
Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.
Evans
S
S
Thomas
C
C
Wang
D
D
Jonas
R A
RA
D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D005260:Female; D005849:Gerbillinae; D007035:Hypothermia / Q000139:chemically induced / Q000503:physiopathology*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*
D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D016291:Dizocilpine Maleate