Reduction of vasogenic edema and infarction by MK-801 in rats after temporary focal cerebral ischemia.
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)
Yang
G
G
Department of Neurosurgery, School of Medicine, University of California, San Francisco.
Chan
P H
PH
Chen
S F
SF
Babuna
O A
OA
Simon
R P
RP
Weinstein
P R
PR
D000818:Animals; D001479:Basal Ganglia / Q000098:blood supply / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D002546:Ischemic Attack, Transient / Q000473:pathology*; D008297:Male; D009460:Neurologic Examination; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate