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

Area of Science:

• Neuroimmunology
• Neuropathology

Background:

• Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
• The integrity of the blood-brain barrier (BBB) is crucial for CNS homeostasis.
• Persistent BBB dysfunction is implicated in MS pathogenesis.

Purpose of the Study:

• To investigate the presence and extent of extravascular serum proteins in longstanding multiple sclerosis plaques.
• To determine the relationship between BBB permeability and demyelination activity in chronic MS lesions.
• To explore the implications of BBB leakage for myelin repair and regeneration.

Main Methods:

• Immunohistochemical examination of 35 MS plaques from five patients.
• Detection of extravascular serum proteins within active and inactive lesions.
• Correlation of protein leakage with histological evidence of demyelination.

Main Results:

• Serum proteins were detected outside blood vessels in the majority of inactive MS plaques (26/34) and the single active lesion.
• Evidence suggests permanent BBB damage in many chronic MS lesions.
• Gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA)-enhanced MRI may underestimate BBB permeability in longstanding plaques.

Conclusions:

• The blood-brain barrier (BBB) is frequently and permanently damaged in chronic multiple sclerosis lesions.
• A compromised BBB is not sufficient to drive active demyelination in MS.
• Persistent leakage of serum factors may hinder oligodendrocyte regeneration and remyelination in longstanding MS plaques.