The role of pericytes in MS pathophysiology.

Abstract

Objective:Our aim was to investigate the impact of pericytes, an important component of the blood brain barrier (BBB), on multiple sclerosis (MS) pathogenesis.Background:Although MS is known as a classical inflammatory demyelinating disorder, the involvement of glial cells in demyelination is increasingly recognized. Vascular pathology has also been recently found to contribute to the pathogenesis of MS. However, the exact mechanisms of this pathology and the influence of pericytes have been scarcely investigated.Design/Methods:Experimental allergic encephalomyelitis (EAE) was induced in C57BL6 mice by myelin oligodendrocyte glycoprotein (MOG) immunization. BBB permeability, number and localization of pericytes were assessed in MS lesions and extracellular matrix components were investigated by immunohistochemical methods.Results:Multiple inflammatory lesions were detected in spinal cord and brain on 40thday of MOG-induced EAE. The lesions contained an abundance of T cells and macrophages and lacked myelin. The BBB permeability increase was shown on EAE lesions by albumin staining. The lesion sites with albumin leakage showed a reduction in PDGFRB+ pericytes and some of the pericytes were found to deviate from the walls of microvessels and be repositioned in the brain parenchyma. Moreover, aSMA+ cells and the extracellular matrix protein content around PDGFRB+ and aSMA+ cells were significantly increased.Conclusions:In this study, we have shown for the first time that EAE lesions show altered pericyte distribution. This alteration is associated with a change in BBB permeability and an increase in extracellular matrix.