Glutamate antagonist MK-801 attenuates incomplete but not complete infarction in thrombotic distal middle cerebral artery occlusion in Wistar rats.
The purpose of this study was to investigate the effects of a non-competitive N-methyl-D-aspartate antagonist, MK-801, on incomplete infarction (selective neuronal necrosis), a zone of which had been found previously in a thrombotic distal middle cerebral artery (MCA) occlusion model in Wistar rats. Male Wistar rats were treated with 1 mg/kg of MK-801 or saline 30 min before MCA occlusion. Laser irradiation with intravenous administration of Rose Bengal dye was used to cause thrombotic distal MCA occlusion. The ipsilateral common carotid artery was occluded permanently and the contralateral carotid artery for 60 min. Head temperature was controlled at 36 degrees C. Cerebral blood flow (CBF) was determined with laser-Doppler flowmetry. Three days after the ischemic insult, brains were perfusion-fixed and volumes of cortical (complete and incomplete) infarction were determined. There were no significant differences in physiological variables or CBF between the two groups. Volumes of complete infarction were equivalent between the two groups (94.9 +/- 15.6 mm3 and 91.6 +/- 14.0 mm3 in the control and MK-801 treated groups, respectively). In MK-801 treated group, the volume of incomplete infarction was reduced by 44% (6.4 +/- 1.7 mm3 vs. 3.6 +/- 2.1 mm3 in control and MK-801 treated groups, respectively, P < 0.05). Although the zone responsive to MK-801 was small in this thrombotic MCA occlusion model, our present study revealed that MK-801 has a beneficial effect on the tissue zone containing selective neuronal alterations (incomplete infarction). Our results support the concept that this drug is effective in the area of less severe ischemia.
Yao
H
H
Department of Neurology, University of Miami School of Medicine, FL 33101.
Markgraf
C G
CG
Dietrich
W D
WD
Prado
R
R
Watson
B D
BD
Ginsberg
M D
MD
D000818:Animals; D002544:Cerebral Infarction / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000502:physiology; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D002542:Intracranial Embolism and Thrombosis / Q000150:complications / Q000188:drug therapy*; D008297:Male; D009336:Necrosis; D009474:Neurons / Q000473:pathology; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
D018691:Excitatory Amino Acid Antagonists; D018377:Neurotransmitter Agents; D018698:Glutamic Acid; D016291:Dizocilpine Maleate