Restoration of Normal Conduction Properties in Demyelinated Spinal Cord Axons in the Adult Rat by Transplantation of Exogenous Schwann Cells

Abstract

Although remyelination of demyelinated CNS axons is known to occur after transplantation of exogenous glial cells, previous studies have not determined whether cell transplantation can restore the conduction properties of demyelinated axons in the adult CNS. To examine this issue, the dorsal columns of the adult rat spinal cord were demyelinated by x-irradiation and intraspinal injections of ethidium bromide. Cell suspensions of cultured astrocytes and Schwann cells derived from neonatal rats transfected with the (β-galactosidase) reporter gene were injected into the glial-free lesion site. After 3–4 weeks nearly all of the demyelinated axons were remyelinated by the transplanted Schwann cells. The dorsal columns were removed and maintained in an in vitro recording chamber; conduction properties were studied using field potential and intra-axonal recording techniques. The demyelinated axons exhibited conduction slowing and block, and a reduction in their ability to follow high-frequency stimulation. Axons remyelinated by transplantation of cultured Schwann cells exhibited restoration of conduction through the lesion, with reestablishment of normal conduction velocity. The axons remyelinated after transplantation showed enhanced impulse recovery to paired-pulse stimulation and greater frequency-following capability as compared with both demyelinated and control axons. These results demonstrate the functional repair of demyelinated axons in the adult CNS by transplantation of cultured myelin-forming cells from the peripheral nervous system in combination with astrocytes.