BLOOD-BRAIN-BARRIER ABNORMALITIES IN LONGSTANDING MULTIPLE-SCLEROSIS LESIONS - AN IMMUNOHISTOCHEMICAL STUDY

Thirty-five randomly selected plaques from five patients with longstan ding multiple sclerosis were examined immunohistochemically for eviden ce of extravascular serum proteins. One lesion showed histological evi dence of active demyelination and 34 were inactive. In the one active lesion and in 26 of the 34 inactive lesions, serum proteins were detec ted outside blood vessels in a distribution consistent with leakage du ring life. The findings suggest that the brood-brain barrier (BBB) is permanently damaged in many old plaques, although to a degree not ofte n detectable by current gadolimium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced magnetic resonance imaging (MRI). The findings als o suggest that in patients with multiple sclerosis, a breached BBB is not by itself sufficient to induce active demyelination. Continuous ex posure of demyelinated axons and glia to cytokines, antibody or other factors present in the circulation might be important, however, in pre venting oligodendrocyte regeneration and new myelin formation in longs tanding lesions.