Netrins and Gene Therapy After Spinal Cord Injury

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DESCRIPTION (provided by applicant): Progress in preclinical research over the last two decades has contributed substantially to our knowledge of factors that can promote axonal growth after spinal cord injury. However, there is a relative paucity of information regarding molecular mechanisms that might augment and guide axonal growth after injury in the adult. One important family of molecules that plays an important role in axon growth and guidance during development is the netrin family of diffusible molecules, and their associated receptors, DCC (deleted colon carcinoma) and UNC-5 family proteins. This project will characterize the natural expression of netrin and its receptors after adult spinal cord injury, then manipulate the potential ability of axons to respond to these molecules using ex vivo gene delivery of netrin to the injured spinal cord. Two specific aims will be examined: Specific Aim 1: Characterize expression of netrins and their receptors (members of the DCC and UNC-5 family) in the intact and lesioned adult rat spinal cord. Specific Aim 2: Determine whether netrin over-expression in the injured adult spinal cord influences the extent or direction of axonal growth.