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

L. Belayev, R. Busto, Weizhao Zhao, Myron Ginsberg, G. Feuerstein

Research output: Contribution to journalArticle

92 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2313-2320
Number of pages8
JournalStroke
Volume26
Issue number12
StatePublished - Jan 1 1995

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Middle Cerebral Artery Infarction
N-Methylaspartate
Brain Ischemia
Brain Edema
Sutures
Lysine
External Carotid Artery
Aptitude
Cannabinoids
Nylons
Internal Carotid Artery
Halothane
HU 211
N-Methyl-D-Aspartate Receptors
Wistar Rats
Perfusion
Brain
Pharmaceutical Preparations

Keywords

  • cerebral ischemia, focal
  • N-methyl-D-aspartate
  • neuroprotection
  • rats

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

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. / Belayev, L.; Busto, R.; Zhao, Weizhao; Ginsberg, Myron; Feuerstein, G.

In: Stroke, Vol. 26, No. 12, 01.01.1995, p. 2313-2320.

Research output: Contribution to journalArticle

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abstract = "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.",
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