Schwann cell remyelination in the multiple sclerosis central nervous system

Multiple sclerosis (MS) is a central nervous system (CNS) demyelinating disease. Failure to successfully remyelinate is common in MS lesions, often with consequent neuronal/axonal damage. CNS myelin is normally made by oligodendroglial cells (OLs). Remyelination by Schwann cells (SchC) has been reported in spinal cord demyelination, where SchCs are in close proximity to CNS myelin. We identified an MS cerebral lesion that was remyelinated by SchCs. This prompted us to query the extent of SchC remyelination in the brains and spinal cords of additional autopsied MS specimens. CNS tissues were obtained from the autopsies of 14 MS cases. Remyelinated lesions were identified by LFB-PAS and solochrome cyanine stainings. Deparaffinized sections containing remyelinated lesions were stained with anti-GFAP to identify reactive astrocytes. P0 is a protein exclusive to peripheral but not CNS myelin. Areas of SchC remyelination were identified by staining with anti-P0. Proteolipid protein (PLP) is Myelinated regions in the index case cerebral lesion were confirmed to be of SchC origin using anti-P0 staining. Subsequently, 64 MS lesions from 14 autopsied MS cases were examined, and 23 lesions in 6 cases showed remyelination by SchCs. Lesions from the cerebrum, brainstem, and spinal cord were examined in each case. When present, SchC remyelination was most commonly located adjacent to venules and was associated with a lower surrounding density of GFAP+ reactive astrocytes than areas of only OL remyelination. The difference was significant only for spinal cord and brainstem lesions but not for lesions located in the brain. In conclusion, we demonstrated SchC remyelination in the cerebrum, brainstem, and spinal cord of 6 autopsied MS cases. To our knowledge, this is the first report of supratentorial SchC remyelination in MS.