The proposed research will employ the chronic, adult rat, complete spinal cord transection model of spinal cord injury. The model is clinically relevant, avoids problems posed by developmental (neonatal lesion) models and is well established in our laboratories. Various palliative strategies will be used to determine the possible responses of and changes in several anatomical and physiological measures following spinal cord injury. These strategies include, a) exercise training, b) fetal spinal cord implants into the transection cavity, c) peripheral nerve grafts bridging the transection, and d) neurotrophic factor-containing nitrocellulose strips implanted in conjunction with fetal tissue implants or nerve grafts. The anatomical measures to be carried out include, a) dorsal root axon regrowth, b) immunocytochemical detection of indoleaminergic fiber regrowth, c) fluorescent dye tracing of axonal regrowth via peripheral nerve grafts, and d) hindlimb muscle fiber size and number. These measures are expected to give an indication of the degree of survivability, tissue reconnection and salutary effects of the various strategies described above on neuronal and muscular tissue below the level of the lesion. The physiological measures to be used include, a) H-reflex monitoring, b) locomotion induced in the decerebrate preparation by stimulation of the mesencephalic locomotor region, and c) locomotion induced by stimulation of the lumbar enlargement in the same preparation. These measures are designed to reveal any gradual changes in reflex function as a result of the various palliative measures, and to determine if locomotion or modulation of spinal pattern generator function occurs following such procedures. this program of research is intended to provide a wide range of normative data in a relevant model of spinal cord injury, as well as probe various possibilities for surgical intervention which might lead to functional improvement following spinal cord trauma. Our preliminary findings provide exciting new indications that the proposed palliative strategies might provide a measure of functional restitution.
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