Importance of oligodendrocyte protection, BBB breakdown and inflammation for remyelination

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the CNS. A better understanding of why remyelination fails in MS is necessary to improve remyelination strategies. Remyelination is mediated by oligodendrocyte precursor cells (OPCs), which are widely distributed throughout the adult CNS. However, it is still unclear whether OPCs detectable in MS lesions survive the inflammatory response but are unable to myelinate or whether OPC and oligodendrocyte death is primarily responsible for remyelination failure and detectable OPCs enter demyelinated areas from adjacent tissue as the lesion evolves. Remyelination strategies should, therefore, focus on stimulation of differentiation or prevention of apoptosis, as well as establishment of a supportive environment for OPC-mediated remyelination, which may be especially important in chronically demyelinated lesions.

Keywords::

• apoptosis
• blood–brain barrier
• demyelination
• inflammation
• multiple sclerosis
• remyelination strategies

Financial & competing interests disclosure

This work was supported by grants from the NIH (NS RO1 32129, NS RO1 507 24180), the National Multiple Sclerosis Society (R63172, CA 1011A8) and the Multiple Sclerosis Research Foundation of Canada (CMS-05). The authors also acknowledge with thanks support from the Applebaum and Hilton Foundations and the Minnesota Partnership Award for Biotechnology and Medical Genomics. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.