Schwann cell remyelination of demyelinated axons in spinal cord multiple sclerosis lesions

Abstract

To investigate remyelination in multiple sclerosis lesions, we immunostained spinal cord sections from patients with multiple sclerosis and neurologically normal (control) patients with antisera to P₀ protein, a major constituent of peripheral nervous system myelin, and myelin basic protein, which is found in both central and peripheral nervous system myelin. In sections from five of the eight patients with no clinical or pathological evidence of neurological disease, P₀ immunostaining was confined to peripheral myelin sheaths in dorsal and ventral roots. They were intensely stained, and peripheral-central nervous system transition zones were clearly demarcated. Sections from the other three control patients contained a few P₀-stained sheaths in the central nervous system near root entry zones or among marginal glia near the dorsal sulcus. Spinal cord sections from six of the ten patients with multiple sclerosis contained clusters of myelin sheaths immunostained by P₀ antiserum. These regenerating sheaths of peripheral nervous system origin were most numerous in large lesions and were commonly located in central areas or peripherally near root entry zones. The sheaths were observed frequently in areas of active demyelination and appeared morphologically normal even when surrounded by debris-filled macrophages. Near margins of small inactive plaques were a few basic protein-stained oligodendroglia extending processes to thin basic protein-stained sheaths. These regenerating sheaths of central origin were relatively uncommon and were not observed in areas of active myelin breakdown. Our observations suggest that Schwann cell remyelination is more extensive in spinal multiple sclerosis lesions than previously thought. In very large spinal cord plaques, Schwann cells also apparently have a more important role in myelin sheath regeneration than do oligodendroglia.