title: Glutamate antagonist therapy reduces neurologic deficits produced by focal central nervous system ischemia.
abstract: Ischemia 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 micrograms (n = 29) in controls to 534 +/- 41.4 micrograms (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.
authors.affiliation: Department of Neurology, Veterans Administration Medical Center, San Diego.
authors.forename: A
authors.initials: A
authors.lastname: Kochhar
authors.forename: J A
authors.initials: JA
authors.lastname: Zivin
authors.forename: P D
authors.initials: PD
authors.lastname: Lyden
authors.forename: V
authors.initials: V
authors.lastname: Mazzarella
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003986:Dibenzocycloheptenes / Q000627:therapeutic use*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate; D018691:Excitatory Amino Acid Antagonists; D002542:Intracranial Embolism and Thrombosis / Q000188:drug therapy* / Q000503:physiopathology; D007511:Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D011817:Rabbits; D013116:Spinal Cord / Q000098:blood supply*
chemical_list: D003986:Dibenzocycloheptenes; D018691:Excitatory Amino Acid Antagonists; D016291:Dizocilpine Maleate