Blood-brain barrier permeability alteration,
vasogenic brain edema, and
infarction, which are more extensive after 3 hours of temporary
middle cerebral artery occlusion (MCAO) and 3 hours of reperfusion than after 6 hours of permanent MCAO, develop in rats after prolonged focal
cerebral ischemia. Protective effects of
excitatory amino acid receptor antagonists have been previously demonstrated after temporary global
ischemia and permanent focal
ischemia in rats. The purpose of this study was to evaluate the effectiveness of
MK-801, a noncompetitive
N-methyl-D-aspartate receptor antagonist, in temporary
middle cerebral artery occlusion in rats maintained at physiological levels of brain temperature. Rats were anesthetized with
chloral hydrate (350 mg/kg, intraperitoneally). The MCAO of rats was occluded by cannulation with a
nylon suture for 3 hours, followed by 3 hours of reperfusion accomplished by withdrawing the
suture.
MK-801 (1 mg/kg, intravenously) or saline (S) was injected immediately before the onset of MCAO. Water content (
MK-801, n = 6; S, n = 6),
Evans blue dye extravasation (
MK-801, n = 6; S, n = 6),
infarct volume (
MK-801, n = 10; S, n = 10), histology (
MK-801, n = 6; S, n = 6), and neurological deficit (
MK-801, n = 15; S, n = 18) were measured at the end of 3 hours of reperfusion. Brain temperature was monitored during the experiment. The
infarction area (measured by 2, 3, 5-
triphenyltetrazolium chloride staining) was reduced (P < 0.001) in the MK-801-treated rats, as was the
infarct volume and the severity of neuronal damage (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)