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

doi:10.1016/0006-8993(94)01433-I

Brain Research

Volume 674, Issue 1, 13 March 1995, Pages 55-62

https://doi.org/10.1016/0006-8993(94)01433-I Get rights and content

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.

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

Abstract

Neuroscience

Brain Res.

J. Neurosci. Methods

Brain Res.

Brain Res.

Elevation of extracellular concentrations of glutamate and aspartate in rat hippocampus during transient cerebral ischemia monitored by intracerebral microdialysis

J. Neurochem.

Ischemic changes in hippocampal CA1 is dependent on glutamate-release and intact innervation from CA3

J. Cerebr. Blood Flow Metab.

Memory and head injury

J. Nerv. Ment. Dis.

Do NMDA antagonists protect against cerebral ischemia: are clinical trials warranted?

Cerebrovasc. Brain Metab. Rev.

HU-211, a non-psychotropic cannabinoid, rescues cortical neurons from excitatory amino acid toxicity in culture

NeuroReport

Non-psychotropic cannabinoid acts as a functionalN-methyl-D-aspartate receptor blocker

Learning in post-traumatic amnesia following extremely severe head injury

Brain Injury

Systemic administration of MK-801 protects against ischemia-induced hippocampal neurodegeneration in gerbil

J. Neurosci.

Cognitive deficits following traumatic brain injury produced by controlled cortical impact

J. Neurotrauma

Assessment of cognitive performance in the Morris water maze following traumatic brain injury

Experimental models of brain injury

J. Neurotrauma