The long-term objective of this researchis to understand the mechanisms underlying the unmasking of latent motor pathways which restore function to muscle paralyzed by spinal cord injury. An animal model of spinal cord injury and plasticity known as the """"""""crossed phrenic phenomenon"""""""" (CPP) is employed to demonstrate that a latent respiratory motor pathway can be activated to restore function to a hemidiaphragm paralyzed by an ipsilateral C2 spinal cord hemisection. Based on new information, a neurotransmitter mediated neuronal-glial interaction may be partially responsiblefor the unmasking of the latent pathway. In addition, the development of two pharmacological methods of activating the latent pathway may lead to improvement of respiratory muscle function not only in our animal model, but also in cervical spinal cord injured humans. There are four specific aims in the present application to test the following hypotheses: 1. that the delayed enhanced expression of the CPPis dependent on serotonin. 2. that serotonin depletion blocks or attenuates the rapid alterations in astrocyte morphology which may be important in the delayed enhanced expression of the CPP. 3. that continuous infusion of a glutamate metabotropic receptor agonist into the subarachnoid space near the medullary chemoreceptor center will not only induce, but also chronically maintain recovery of a hemidiaphragm previously paralyzed by cervical spinal cord injury. 4. that either oral or intravenously administered theophylline will significantly improve respiratory muscle function following cervical spinal cord injury in man.
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