Extensive extracellular matrix depositions in active multiple sclerosis lesions

Abstract

In the central nervous system, basement membrane (BM) constituents are predominantly associated with the vasculature. However, under inflammatory conditions, the expression of BM components may alter. Here, we investigated the distribution of several BM components, including laminin, collagen type IV and heparan sulfate proteoglycans in various multiple sclerosis (MS) lesions. We observed irregular and discontinuous BMs in active lesions. Throughout active MS lesions, we found dense networks of BM proteins, which were surprisingly not associated with the cerebrovasculature. These striking parenchymal networks were not observed in chronic inactive MS lesions and brains of non-neurological controls. In addition, we studied the distribution of transforming growth factor-β1 (TGF-β1), since it is known as a major modulator of ECM production. Leukocytes, in particular CD68-positive macrophages, expressed high levels of TGF-β1 and were located in close proximity to parenchymal BM deposits in the MS lesions. We postulate that these BM networks may play a role in the further recruitment of inflammatory cells and form a barrier for axonal regeneration.

Keywords

• Basement membrane
• Blood–brain barrier
• Macrophages
• Multiple sclerosis
• Transforming growth factor-β1