The long-term objectives of this project are to evaluate functional consequences of spinal cord injury (SCI) and of fetal tissue transplants at previous injury sites in cats and rats. The injury models (spinal contusion or compression) to be used mimic many features of SCI in humans. The techniques for functional evaluation have been developed by this group of researchers, and these methods have shown that a central core spinal lesion caused by contusion/compression represents the minimal spinal trauma responsible for spasticity, which often is a hallmark consequence of SCI. The proposed experiments will further evaluate the effects of SCI on spinal reflexes and will determine mechanisms for generation, maintenance and attenuation of spasticity. Also, we have shown in other studies that transplantation can attenuate the development of hyperreflexia following SCI. The proposed experiments will test how this graft-associated effect is governed by various lesion conditions such as injury-to-graft delay interval and proximity of the injury/graft site relative to the lumbar motoneuron pool. The use of behavioral methods of reflex assessment in awake animals will provide quantitative monitoring of the time-course of changes in functional integrity of spinal cord circuitry caudal to compression injury (with or without a transplant). Additional physiological measures will identify the modulatory capabilities of spinal circuits caudal to a lesion (with or without a transplant), and the importance of these data will be greatly enhanced by knowledge of the reflex excitability of each animal, as characterized behaviorally. Experiments with cats will take advantage of kinematic analyses to relate the time-course of changes in hindlimb locomotor capacities to the progression of single limb reflex abnormalities following thoracic compression injury with or without transplantation. Experiments in cats and rats will evaluate the effects of transplantation soon after SCI that could favor protective effects preventing secondary degeneration over time, as compared with late transplantation which would be more directed at the restorative capacities of transplantation. Experiments in rats will provide additional comparisons between the effects of lumbar compression injuries and transplants (that occur near the segmental circuitry mediating hindlimb reflexes) and thoracic injuries and transplants (that occur remotely rostral to the lumbosacral hindlimb circuitry). Overall, these experiments will provide a comprehensive analysis of: 1) the effects of central cord injuries on the functional status of spinal cord circuits near and remote to the injury and 2) lesion variables that could influence desirable effects of transplantation on near and remote spinal circuits.
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