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Volume 16, Number 10,
Issue of May 15, 1996
pp. 3199-3208
Copyright ©1996 Society for Neuroscience
Restoration of Normal Conduction Properties in Demyelinated
Spinal Cord Axons in the Adult Rat by Transplantation of Exogenous
Schwann Cells
Received Nov. 10, 1995; revised Feb. 7, 1996; accepted Feb. 12, 1996.
Osamu Honmou,
Paul A. Felts,
Stephen G. Waxman, and
Jeffery D. Kocsis
Department of Neurology, Yale University School of Medicine, New
Haven, Connecticut 06516, and PVA/EPVA Neuroscience Research Center, VA
Medical Center, West Haven, Connecticut 06516
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 ( -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.
Key words:
demyelination;
remyelination;
cell
transplantation;
Schwann cells;
astrocytes;
restoration of
conduction
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