Long-term effect of HU-211, a novel non-competitive NMDA antagonist, on motor and memory functions after closed head injury in the rat

Long-term effect of HU-211, a novel non-competitive NMDA antagonist, on motor and memory... HU-211 is a synthetic, non-psychotropic cannabinoid which acts as a non-competitive NMDA antagonist and antioxidant. We studied the drug's therapeutic window as well as its long-term effect on cognitive and motor functions in a model of closed head injury (CHI) in the rat. A weight-drop device was used to induce CHI in ether anesthetized male rats. HU-211 (5 mg/kg) was administered i.v. to the experimental groups. For the therapeutic window study, drug was injected at 4 or 6 h after CHI. Edema (water content) and clinical status (neurological severity score, NSS) were evaluated at 24 h. Reduction of edema was slight, whereas improvement of NSS was significant when the drug was administered at 4 or 6 h ( P = 0.0023and0.059 , respectively). To determine the drug's long-term effect, it was administered 1 h after CHI and additional doses were later given. NSS was evaluated for a period of 30 d. A single dose of HU-211 given 1 h post-CHI improved the clinical outcome during the 30 d period ( P < 0.01 ). Repetitive doses of HU-211 injected during the post traumatic period had similar effects. Cognitive functions were evaluated in the Morris water maze, with rats trained either before or after CHI. CHI resulted in a highly significant impairment of these abilities, whereas HU-211 treatment 1 h after CHI improved performance. Our results indicate that HU-211 is a potent cerebroprotective agent, with a therapeutic window of about 4 h. The beneficial response obtained even after a single dose was long lasting, and ameliorated impairment of both motor and cognitive functions following CHI. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Brain Research Elsevier

Long-term effect of HU-211, a novel non-competitive NMDA antagonist, on motor and memory functions after closed head injury in the rat

Brain Research, Volume 674 (1) – Mar 13, 1995

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Publisher
Elsevier
Copyright
Copyright © 1995 Elsevier Science B.V. All rights reserved
ISSN
0006-8993
D.O.I.
10.1016/0006-8993(94)01433-I
Publisher site
See Article on Publisher Site

Abstract

HU-211 is a synthetic, non-psychotropic cannabinoid which acts as a non-competitive NMDA antagonist and antioxidant. We studied the drug's therapeutic window as well as its long-term effect on cognitive and motor functions in a model of closed head injury (CHI) in the rat. A weight-drop device was used to induce CHI in ether anesthetized male rats. HU-211 (5 mg/kg) was administered i.v. to the experimental groups. For the therapeutic window study, drug was injected at 4 or 6 h after CHI. Edema (water content) and clinical status (neurological severity score, NSS) were evaluated at 24 h. Reduction of edema was slight, whereas improvement of NSS was significant when the drug was administered at 4 or 6 h ( P = 0.0023and0.059 , respectively). To determine the drug's long-term effect, it was administered 1 h after CHI and additional doses were later given. NSS was evaluated for a period of 30 d. A single dose of HU-211 given 1 h post-CHI improved the clinical outcome during the 30 d period ( P < 0.01 ). Repetitive doses of HU-211 injected during the post traumatic period had similar effects. Cognitive functions were evaluated in the Morris water maze, with rats trained either before or after CHI. CHI resulted in a highly significant impairment of these abilities, whereas HU-211 treatment 1 h after CHI improved performance. Our results indicate that HU-211 is a potent cerebroprotective agent, with a therapeutic window of about 4 h. The beneficial response obtained even after a single dose was long lasting, and ameliorated impairment of both motor and cognitive functions following CHI.

Journal

Brain ResearchElsevier

Published: Mar 13, 1995

References

  • Elevation of extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis
    Benveniste, H.; Drejer, J.; Schousboe, A.; Diemer, N.H.
  • Brain phospholipase A 2 is activated after experimental closed head injury in rats
    Shohami, E.; Shapira, Y.; Yadid, G.; Reisfeld, N.; Yedgar, S.

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