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Abha Kochhar, PhD; Justin A. Zivin, MD, PhD; Patrick D. Lyden, MD; Vincent Mazzarella

Arch Neurol. 1988;45(2):148-153.

Abstract
• lschemia may increase synaptic concentrations of glutamate, which may cause neuronal damage. Drugs that antagonize glutamate's effects may reduce this type of damage. MK-801, an N-methyl-D-aspartate receptor antagonist that readily enters the central nervous system, was evaluated in two focal central nervous system ischemia models: a multiple cerebral embolic model and a rabbit spinal cord ischemia model. When animals were treated five minutes after the onset of injury, MK-801 was effective in reducing ischemic damage in both models. In the multiple cerebral embolic model, the average dose of microspheres trapped in the brain increased from 344.8 ± 51.4 µg (n = 29) in controls to 534 ± 41.4 µg (n = 17) in the MK-801-treated group. Similarly, in the rabbit spinal cord ischemia model, the average ischemia duration increased from 28.9 ± 1.7 minutes (n = 52) in controls to 50.6 ± 3.9 minutes (n = 12) in the MK-801-treated group. These results suggest that this glutamate antagonist should be useful for the treatment of stroke.

Author Affiliations
From the Department of Neurology, Veterans Administration Medical Center, San Diego (Drs Zivin and Lyden), and Department of Neurosciences, University of California-San Diego, School of Medicine, La Jolla (Drs Kochhar, Zivin, and Lyden and Mr Mazzarella).

Footnotes
Accepted for publication Sept 18, 1987.

Read in part at the annual meeting of the American Academy of Neurology, New York, April 8, 1987.

Reprint requests to Department of Neurosciences, M-024, University of California-San Diego, School of Medicine, La Jolla, CA 92093 (Dr Zivin).

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