TY - JOUR
T1 - Hu-211, a novel noncompetitive n-methyl-d-aspartate antagonist, improves neurological deficit and reduces infarct volume after reversible focal cerebral ischemia in the rat
AU - Belayev, Ludmila
AU - Busto, Raul
AU - Zhao, Weizhao
AU - Ginsberg, Myron D.
PY - 1995/12
Y1 - 1995/12
N2 - Background and Purpose: HU-211 is a nonpsychotropic cannabinoid analogue that has been shown to act as a functional N-methyl-D-aspartate receptor blocker. We investigated the neuroprotective efficacy of HU-211 in a model of reversible middle cerebral artery occlusion (MCAo) in rats. Methods: Male Wistar rats were anesthetized with halothane and subjected to 90 minutes of temporary MCAo by retrograde insertion of an intraluminal nylon suture, coated with poly-L-lysine, through the external carotid artery into the internal carotid artery and MCA. The drug (HU-211 in cosolvent, 4 mg/kg IV) or vehicle was administered in a blinded fashion 70 minutes after onset of MCAo. Behavioral tests were evaluated during occlusion (60 minutes) and for a 3-day period after MCAo. Three days after MCAo, brains were perfusion-fixed, and infarct volumes were determined. Results: HU-211 significantly improved the neurological score compared with vehicle during the 3 days after MCAo. Treatment with HU-211 also significantly reduced both infarct volume (mean±SEM, 66.6±12.5 versus 149.8±36.3 mm3) and brain swelling (2.61±1.33% versus 6.66±1.24%) compared with vehicle-treated rats (n=17 in each group). Conclusions: These results demonstrate the neuroprotective ability of HU-211 in focal cerebral ischemia as judged by neurological score, infarct size, and brain swelling. Reversible MCAo with the use of a poly-L- lysine-coated intraluminal suture proved to be a reliable and effective modification of this technique, yielding consistent results.
AB - Background and Purpose: HU-211 is a nonpsychotropic cannabinoid analogue that has been shown to act as a functional N-methyl-D-aspartate receptor blocker. We investigated the neuroprotective efficacy of HU-211 in a model of reversible middle cerebral artery occlusion (MCAo) in rats. Methods: Male Wistar rats were anesthetized with halothane and subjected to 90 minutes of temporary MCAo by retrograde insertion of an intraluminal nylon suture, coated with poly-L-lysine, through the external carotid artery into the internal carotid artery and MCA. The drug (HU-211 in cosolvent, 4 mg/kg IV) or vehicle was administered in a blinded fashion 70 minutes after onset of MCAo. Behavioral tests were evaluated during occlusion (60 minutes) and for a 3-day period after MCAo. Three days after MCAo, brains were perfusion-fixed, and infarct volumes were determined. Results: HU-211 significantly improved the neurological score compared with vehicle during the 3 days after MCAo. Treatment with HU-211 also significantly reduced both infarct volume (mean±SEM, 66.6±12.5 versus 149.8±36.3 mm3) and brain swelling (2.61±1.33% versus 6.66±1.24%) compared with vehicle-treated rats (n=17 in each group). Conclusions: These results demonstrate the neuroprotective ability of HU-211 in focal cerebral ischemia as judged by neurological score, infarct size, and brain swelling. Reversible MCAo with the use of a poly-L- lysine-coated intraluminal suture proved to be a reliable and effective modification of this technique, yielding consistent results.
KW - cerebral ischemia, focal
KW - N-methyl-D-aspartate
KW - neuroprotection
KW - rats
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U2 - 10.1161/01.str.26.12.2313
DO - 10.1161/01.str.26.12.2313
M3 - Article
C2 - 7491657
AN - SCOPUS:0028884634
VL - 26
SP - 2313
EP - 2319
JO - Stroke
JF - Stroke
SN - 0039-2499
IS - 12
ER -