Importance of oligodendrocyte protection, BBB breakdown and inflammation for remyelination

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.