Blood-brain barrier abnormalities in longstanding multiple sclerosis lesions. An immunohistochemical study

Thirty-five randomly selected plaques from five patients with longstanding multiple sclerosis were examined immunohistochemically for evidence of extravascular serum proteins. One lesion showed histological evidence of active demyelination and 34 were inactive. In the one active lesion and in 26 of the 34 inactive lesions, serum proteins were detected outside blood vessels in a distribution consistent with leakage during life. The findings suggest that the blood-brain barrier (BBB) is permanently damaged in many old plaques, although to a degree not often detectable by current gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced magnetic resonance imaging (MRI). The findings also suggest that in patients with multiple sclerosis, a breached BBB is not by itself sufficient to induce active demyelination. Continuous exposure of demyelinated axons and glia to cytokines, antibody or other factors present in the circulation might be important, however, in preventing oligodendrocyte regeneration and new myelin formation in longstanding lesions.