TY - JOUR T1 - MK-801 Limits Neurovascular Dysfunction during Experimental Allergic Encephalomyelitis JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 397 LP - 402 VL - 282 IS - 1 AU - Christopher Bolton AU - Carolyn Paul Y1 - 1997/07/01 UR - http://jpet.aspetjournals.org/content/282/1/397.abstract N2 - Increased permeability of the blood-brain barrier (BBB) is a characteristic of the demyelinating disease multiple sclerosis and the animal counterpart experimental allergic encephalomyelitis (EAE). In physically traumatized cerebral tissue neurovascular damage, linked with activation of the cerebroendothelial-bound N-methyl-d-aspartate receptor, can be treated with the antagonist MK-801. We have examined the ability of MK-801 to modify BBB leakage and the development of disease during EAE. Prophylactic MK-801, at 0.15 mg kg− 1 body weight suppressed neurovascular breakdown, measured by a dual radioisotope technique, and significantly reduced neurological deficits (P < .05), but not perivascular lesions. A 2-fold increase in administered MK-801 completely prevented abnormal extravasation in cerebella (P < .01) and significantly inhibited BBB disruption in medulla-pons (P < .05) and cervical spinal tissues (P < .01). High-dose treatment also restricted disease development (P < .01) and lesion formation (P < .05). Therapeutic MK-801, at 0.30 mg kg− 1 body weight, completely counteracted neuroendothelial leakage in cerebella (P < .05) and inhibited BBB dysfunction in remaining tissues without restricting inflammatory cell invasion. However, doubling the dose did not further enhance suppression of neurovascular breakdown. Our use of MK-801 to control major features of EAE strongly implicates N-methyl-d-aspartate receptor-dependent mechanisms in disease development and prompts consideration of a role for the receptor in the pathogenesis of human demyelinating conditions. The American Society for Pharmacology and Experimental Therapeutics ER -