Remyelination of CNS axons by Schwann cells transplanted from the sciatic nerve

Abstract

SCHWANN cells can remyelinate axons normally myelinated by oligodendrocytes, after either primary demyelination^1–3 or suppression of myelination by X irradiation at the time of myelination^4,5. It has been suggested that the glial limiting membrane normally inhibits Schwann cell invasion of the CNS (ref. 2) and its reformation inhibits uncontrolled invasion by Schwann cells once this phenomenon has been initiated^1,2. The Schwann cells in these situations are thought to arise from the nerve roots. I undertook experiments to determine whether it is possible to suppress remyelination following primary demyelination in an experimental animal. If so the resulting demyelinated axons would be similar to those present in the multiple sclerosis plaque, that is they would remain demyelinated unrepaired by glial or Schwann cells. Using such a lesion it would then be possible to establish if Schwann cells obtained from a source outside the central neuraxis would remyelinate these axons. In the past, attempts at transplanting peripheral nervous tissue into the central nervous system have shown very limited invasion of peripheral elements into the neuropil of the CNS (refs. 6,7) and it was hoped that the presence of large numbers of demyelinated axons would act as a stimulus for Schwann cell invasion⁸. In addition, intraspinal injections of lysolecithin facilitate Schwann cell invasion of the CNS from local sources^2,9. By abolishing this intrinsic Schwann cell remyelination potential and by substituting an extrinsic source of Schwann cells it might be possible to determine if persistently demyelinated axons in the CNS, similar to those in multiple sclerosis plaques, can be repaired by outside interference. I report here the preparation of areas of demyelination in rats and cats which remyelinated only in the presence of added Schwann cells.