Can transplantation of neurons facilitate motor recovery in paraplegics? Study of an animal model

This review strives forward at least two goals. First, to take from the literature the arguments demonstrating that hindlimbs locomotion is controlled by a spinal network of neurons (the so-called Central Pattern Generator for locomotion--CPG) known to be able to generate locomotor activity independently of the control of supraspinal nervous structures, as it is after thoracic lesions of the spinal cord. The principles of work of the CPG and its intrinsic possibilities to adapt its working are reviewed. Special reference is made to the various ways used during experiments to activate the CPG in spinal animals or clinical practice in paraplegic men: training to walk, electrical stimulations, pharmacological stimulations. Second, to show, from our own results, obtained from the study of an animal model of paraplegia, the adult spinal rat, how it could be possible to take advantage of the autonomy of the CPG, with special reference to its sensibility to monoamines, to obtain locomotor recovery in hindlimbs after section of the thoracic spinal cord, by means of transplantation of noradrenergic and/or serotonergic embryonic neurons in the lumbo-sacral spinal cord. Section of the spinal cord at a thoracic level results in an important locomotor deficit in hindlimbs, likely linked to degeneration of monoaminergic terminals in the lumbar enlargement. In the adult spinal rat, sub-lesional injection of a suspension of embryonic nervous cells, taken from either locus coeruleus or raphe sites, leads to reinnervation of the lumbar enlargement with monoaminergic terminals. Despite the fact that connections with supraspinal structures are not reestablished, transplanted animals recover progressively a posture convenient for locomotion. The hindlimbs, which are in an extended position a few days after the lesion, become progressively flexed and able to support the body weight. This evolution does not appear in spinal but non transplanted animals. But, the main point is that transplanted animals develop, within the few weeks that follow transplantation, a good-quality locomotor activity in hindlimbs which had no equivalent in spinal but non transplanted animals. The reality of a lumbar CPG for locomotion and the efficacy of pharmacological treatments and training to walk, to elicit recovery of stepping, are discussed in man, in connection with the relevance to use transplantation of monoaminergic nervous cells in the spinal cord of paraplegics.