RESTORATION OF NORMAL CONDUCTION PROPERTIES IN DEMYELINATED SPINAL-CORD AXONS IN THE ADULT-RAT BY TRANSPLANTATION OF EXOGENOUS SCHWANN-CELLS

Although remyelination of demyelinated CNS axons is known to occur aft er transplantation of exogenous glial cells, previous studies have not determined whether cell transplantation can restore the conduction pr operties 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 su spensions of cultured astrocytes and Schwann cells derived from neonat al rats transfected with the (beta-galactosidase) reporter gene were i njected into the glial-free lesion site. After 3-4 weeks nearly all of the demyelinated axons were remyelinated by tie transplanted Schwann cells. The dorsal columns were removed and maintained in an in vitro r ecording chamber; conduction properties were studied using field poten tial and intra-axonal recording techniques. The demyelinated axons exh ibited conduction slowing and block, and a reduction in their ability to follow high-frequency stimulation. Axons remyelinated by transplant ation of cultured Schwann cells exhibited restoration of conduction th rough the lesion, with reestablishment of normal conduction velocity. The axons remyelinated after transplantation showed enhanced impulse r ecovery to paired-pulse stimulation and greater frequency-following ca pability as compared with both demyelinated and control axons. These r esults 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.