Improving the motor recovery after central nervous system injury remains an important but not fully recognized clinical goal. This proposal seeks to provide new insights into the area of clinical motor recovery by studying the functional recovery and anatomical rearrangements following corticospinal tract lesions in adult, male, Sprague-Dawley rats. In rodents, as in man, the corticospinal tracts (CST) mediate finely coordinated movements of the forepaws. Normal adult rats are trained to use these forepaw skills to retrieve small food pellets from within narrow slots. Rats with bilateral CST lesions lose and do not regain the ability to perform this task. Rats with unilateral CST lesions also suffer a loss of performance with the affected forepaw, but do exhibit some recovery of motor control. Although the mechanism of recovery in the rats with unilateral lesions is unknown, it is possible that the undamaged CST may be important in mediating this recovery. Therefore, in the initial set of experiments rats that have recovered from unilateral CST lesions will undergo lesioning of the remaining CST. Postoperatively their ability to perform finely coordinated forepaw movements will be compared to their preoperative performance and to sham-operated controls. In the second set of experiments, the effects of a series of pharmacological agents (i.e. gangliosides, bicuculline, baclofen, steroids, etc.) and intensive retraining will be assessed in rats that have received bilateral and unilateral CST lesions. The purpose of these experiments is to identify any agents that may enhance clinical recovery from motor lesions. The third set of experiments will be devoted to assessing the anatomical rearrangement of other axon pathways after CST injury. These will involve studying the undamaged CST, both rubrospinal tracts, the vestibulospinal tracts and dorsal roots with anterograde and retrograde axonal tracing agents to determine if synaptic rearrangement occurs after CST injury. In addition, the effect of CST injury on laminin production by astrocytes in the spinal cord will be assessed to determine if laminin production by spinal cord astrocytes may mediate synaptic arrangement. This proposal seeks to identify the anatomical rearrangements that occur after injury to a central motor pathway and to identify possible means of enhancing this recovery which might be applicable to the human clinical situation.
