Glutamate Antagonist Therapy Reduces Neurologic Deficits Produced by Focal Central Nervous System Ischemia

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.