Progress has been made over the last decade in understanding mechanisms and consequences of injury to the CNS and in augmenting CNS plasticity and regeneration after experimental spinal cord injury (SCI) in non-primates. The potential relevance of this work to injured primate systems remains to be established. Differences between primates and rodents in the anatomy and function of neural systems, and in immune and inflammatory responses to injury, could complicate the simple translation of findings from lower to higher species. This project aims to address these issues by bringing together investigators with expertise and established records in examining the rodent, non-human primate, and human spinal cord. Work will specifically focus on developing a reliable and practical model with which to study SCI in primates. Work will then proceed to examine two specific interventions that have been shown to improve plasticity and function in rodent models: neurotrophic factor gene therapy and experience-dependent plasticity. Synergy between these interventions will be examined in a final aim. In addition, the project will overall begin the process of gathering safety data for the eventual translation of therapies to humans. Collectively, this work will contribute knowledge at both mechanistic and practical levels for the development and testing of therapeutic strategies for promoting recovery from primate SCI. The following Aims will be studied.
Specific Aim 1 : Establish a Model of Primate SCI.
Specific Aim 2 : Determine if Growth Factor Gene Therapy Augments Plasticity and/or Regeneration After Primate SCI.
Specific Aim 3 : Experience-Dependent Plasticity: A) Effects of Motor Activity on Spinal Cord Plasticity and Function After Injury. B) Synergy Between Motor Activity and Growth Factor Gene Therapy in Promoting Recovery After Primate SCI.
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