Stroke, Vol 24, 864-870, Copyright © 1993 by American Heart Association
H Yao, MD Ginsberg, BD Watson, R Prado, WD Dietrich, S Kraydieh and R Busto
BACKGROUND AND PURPOSE: We examined the effects of the noncompetitive N-
methyl-D-aspartate receptor antagonist MK-801 using a newly developed
stroke model of thrombotic distal middle cerebral artery occlusion under
conditions of carefully controlled head temperature. METHODS: Male
Sprague-Dawley rats were treated with 1 mg/kg of MK-801 or saline before
the induction of ischemia. An argon laser-activated dye laser (562 nm) was
used to cause thrombotic distal middle cerebral artery occlusion. In
experiments 1 and 2, the single laser beam (20 mW) was separated into three
beams. Each beam was positioned onto the distal middle cerebral artery at
three sites along the vessel. The photosensitizing dye rose bengal (20
mg/kg) was administered intravenously over 2 minutes; the three points were
then irradiated for 3 minutes. In experiment 3, higher power of the laser
(three separate irradiations using a single beam of 20 mW) was used. The
ipsilateral common carotid artery was occluded permanently, and the
contralateral carotid artery was occluded for 60 minutes. Head temperature
was controlled at 36 degrees C in experiment 1 and not controlled in
experiments 2 and 3. Three days after the ischemic insult, brains were
perfusion-fixed and infarct volumes were determined. RESULTS: Head
temperature was mildly hypothermic (34-35 degrees C before ischemia, with a
further decrease of 1-2 degrees C during the initial 60 minutes of
ischemia) in experiment 2. However, no differences were observed in head
temperature between the MK-801-treated and control groups. Cortical infarct
volume in experiment 1 was 89 +/- 29 mm3 (mean +/- SD) in the treated
group, which was not different from the control value of 84 +/- 40 mm3.
Infarct volumes were smaller (58 +/- 35 mm3 and 54 +/- 14 mm3) in the
control groups of experiments 2 and 3, respectively. However, MK-801 also
failed to reduce infarct volumes in experiments 2 and 3. CONCLUSIONS:
MK-801 is not effective in this stroke model of focal thrombotic infarction
under conditions of either controlled (normothermic) or uncontrolled
(mildly hypothermic) head temperature.
ARTICLES
Failure of MK-801 to reduce infarct volume in thrombotic middle cerebral artery occlusion in rats
Department of Neurology, University of Miami School of Medicine, Florida 33101.
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