Adult human spinal cord injury (SCI) leads to sensory, motor, and autonomic dysfunctions. This project represents a multi-disciplinary approach to a long-term objective of developing a therapeutic strategies for functionally repairing the dorsal column-dorsal column nucleic sensory pathway in both acute and chronic cervical SCI. To improve sensory function in humans with cervical SCI, it is hypothesized that injury sensory axons need to regenerate, reinnervate their target sites, and make functional synapses with their target neurons. To test this hypothesis, we are using an adult rat model of mid-cervical SCI and are focusing on ascending primary afferent axons within the dorsal columns of forepaw dorsal root ganglion neurons. Our preliminary data demonstrate that some acutely injured forepaw primary afferent axons regenerate through extraspinal sciatic nerve graft bridges between the mid-cervical spinal cord dorsal columns and brainstem to form functional synapses with target brainstem dorsal column nucleic neurons. In this project, we will use anatomical electrophysiological, and behavioral testing techniques to 1) optimize strategies for increasing regeneration of acutely injured forepaw primary afferent axons within sciatic nerve grafts, 2) develop effective strategies for increasing acutely injured forepaw primary afferent axons outgrowth from sciatic nerve grafts into their target brainstem dorsal column nuclei, and to 3) determine whether regenerating chronically injured forepaw primary afferent axons form functional synapses with target dorsal column nuclei neurons. The significance of this project is that it will delineate a treatment strategy for sensory dysfunction after cervical SCI that if successful in acute and chronic SCI models may be implemented clinically.
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