Inhibition of blood-brain barrier disruption in experimental allergic encephalomyelitis by short-term therapy with dexamethasone or cyclosporin A.
Double radioisotope measurement of neurovascular integrity in Lewis rats inoculated for experimental allergic encephalomyelitis (EAE) showed abnormal elevation of albumin extravasation in the cerebellum, medulla-pons and cervical spinal cord at the time of clinical manifestation. Therapeutically administered dexamethasone (Dex) (0.1-1 mg/kg body weight) or cyclosporin A (CsA) (25-75 mg/kg body weight) dose-dependently reduced albumin movement across the blood-brain barrier (BBB). Dex at a dose of 1 mg/kg completely suppressed abnormal BBB permeability in all tissues (P < or = 0.001), while CsA at the highest dose of 75 mg/kg achieved highly significant (P < or = 0.001), but not complete, suppression of aberrant barrier leakage in the areas studied. The implications of these findings to possible drug action at the immunocompromised cerebrovasculature are discussed.
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002199:Capillary Permeability / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects; D016572:Cyclosporine / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000187:drug effects; D008297:Male; D011506:Proteins / Q000187:drug effects; D051381:Rats; D011917:Rats, Inbred Lew
D011506:Proteins; D003907:Dexamethasone; D016572:Cyclosporine