INHIBITION OF BLOOD-BRAIN-BARRIER DISRUPTION IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS BY SHORT-TERM THERAPY WITH DEXAMETHASONE OR CYCLOSPORINE-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 less than or equal to 0.001), while CsA at the highest dose of 75 mg/kg achieved highly significant (P less than or equal to 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.