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 clinica l treatment for human demyelinating diseases because of its demonstrated ef ficacy in remyelinating experimentally demyelinated axons. As a step toward s clinical application it is necessary to demonstrate that the procedure is safe and efficacious in promoting behavioural recovery, In this study we t ransplanted glial cell progenitors into demyelinating lesions induced by in traspinal injection of ethidium bromide in the rat. Locomotor function afte r transplantation was assessed using a beam-walking test that has previousl y been shown able to detect deficits associated with demyelination in the d orsal funiculus of the rat spinal card. Two groups of animals with transpla nts 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 receipients, permitting their identification by use of a probe specific to the rat Y chromosome. Fo llowing transplantation, there was severe axon loss in a large proportion o f the irradiated animals and those affected did not recover normal behaviou ral function. In contrast, both the small proportion of the irradiated grou p that sustained only mild axon loss and the nonirradiated recipients of tr ansplants recovered normal function on our behavioural test. We conclude th at glial cell transplantation is able to reverse the functional deficits as sociated with demyelination, provided axonal loss is minimal.