Behavioural consequences of oligodendrocyte progenitor cell transplantation into experimental demyelinating lesions in the rat spinal cord.
Glial cell transplantation has the potential to be developed into a clinical treatment for human demyelinating diseases because of its demonstrated efficacy in remyelinating experimentally demyelinated axons. As a step towards clinical application it is necessary to demonstrate that the procedure is safe and efficacious in promoting behavioural recovery. In this study we transplanted glial cell progenitors into demyelinating lesions induced by intraspinal injection of ethidium bromide in the rat. Locomotor function after transplantation was assessed using a beam-walking test that has previously been shown able to detect deficits associated with demyelination in the dorsal funiculus of the rat spinal cord. Two groups of animals with transplants were examined. In one group, spontaneous remyelination was prevented by exposure of the lesion to 40 Gy of X-irradiation; in the other, male glial cells were transplanted into nonirradiated female recipients, permitting their identification by use of a probe specific to the rat Y chromosome. Following transplantation, there was severe axon loss in a large proportion of the irradiated animals and those affected did not recover normal behavioural function. In contrast, both the small proportion of the irradiated group that sustained only mild axon loss and the nonirradiated recipients of transplants recovered normal function on our behavioural test. We conclude that glial cell transplantation is able to reverse the functional deficits associated with demyelination, provided axonal loss is minimal.
Jeffery
N D
ND
Department of Clinical Veterinary Medicine, University of Cambridge, UK. ucgandj@ucl.ac.uk
Crang
A J
AJ
O'leary
M T
MT
Hodge
S J
SJ
Blakemore
W F
WF
D000818:Animals; D001369:Axons / Q000502:physiology; D001522:Behavior, Animal / Q000502:physiology; D016380:Brain Tissue Transplantation; D002540:Cerebral Cortex / Q000166:cytology; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology / Q000601:surgery*; D004996:Ethidium; D005260:Female; D008297:Male; D018733:Nicotinic Antagonists; D009836:Oligodendroglia / Q000637:transplantation*; D011833:Radiation Injuries, Experimental / Q000601:surgery; D051381:Rats; D011917:Rats, Inbred Lew; D013116:Spinal Cord / Q000473:pathology / Q000528:radiation effects / Q000601:surgery; D033581:Stem Cell Transplantation
D018733:Nicotinic Antagonists; D004996:Ethidium