This Program Project represents a multi-disciplinary approach to investigating the pathophysiology of spinal cord injury (SCI), with the overall goal of developing therapeutic strategies directed at both the acute and chronic injury setting. Project 1 will investigate specific pathophysiology processes that may be targeted with acute neuroprotective strategies. Specifically, the effects of contusive SCI on apoptotic and necrotic cell injury will be assessed and therapeutic strategies, including neurotrophic factor and cytokine treatment, will be tested. The studies proposed in Project 2 will investigate novel immediate and delayed strategies to promote axonal tract regeneration and functional reinnervation of target neurons following SCI. The strategies include the combination of bridging permissive substrates (neurotrophin-engineered Schwann cells) with neuroprotective agents, neurotrophic factors, and unsheathing glia. In Project 3, the potential of utilizing CNS sem cell therapy for SCI will be studied. Pluripotent CNS stem cells whose fate can be precisely controlled in vitro will be transplanted into the injured cord to myelinate axons, to promote axonal regeneration, to reconstruct circuitry, to replace neurons, and restore function. Project 4 will make use of human spinal cord specimens to help identify cellular signals associated with subacute and chronic SCI histopathology. Specifically, this project will investigate which of the cellular and molecular responses observed in experimental animals are applicable to humans, and whether these responses are related to severity and outcome of CNS injury. The Program Project is supported by an established group of scientists who will provide the expertise necessary to conduct this multi-disciplinary program of SCI. Together, these experimental studies should enhance our understanding of the critical events associated with acute and chronic SCI and help to identify novel treatment strategies to promote neuroprotection, axonal regeneration, neuron replacement, myelination, and recovery of function in human SCI.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
3P01NS038665-03S1
Application #
6592652
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Chiu, Arlene Y
Project Start
2000-07-01
Project End
2005-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
3
Fiscal Year
2002
Total Cost
$69,269
Indirect Cost
Name
University of Miami School of Medicine
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
City
Miami
State
FL
Country
United States
Zip Code
33146
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Flora, Govinder; Joseph, Gravil; Patel, Samik et al. (2013) Combining neurotrophin-transduced schwann cells and rolipram to promote functional recovery from subacute spinal cord injury. Cell Transplant 22:2203-17
Williams, Ryan R; Pearse, Damien D; Tresco, Patrick A et al. (2012) The assessment of adeno-associated vectors as potential intrinsic treatments for brainstem axon regeneration. J Gene Med 14:20-34
Hill, Caitlin E; Brodak, Danika M; Bartlett Bunge, Mary (2012) Dissociated predegenerated peripheral nerve transplants for spinal cord injury repair: a comprehensive assessment of their effects on regeneration and functional recovery compared to Schwann cell transplants. J Neurotrauma 29:2226-43
Maggio, Dominic M; Chatzipanteli, Katina; Masters, Neil et al. (2012) Acute molecular perturbation of inducible nitric oxide synthase with an antisense approach enhances neuronal preservation and functional recovery after contusive spinal cord injury. J Neurotrauma 29:2244-9
Hill, Caitlin E; Guller, Yelena; Raffa, Scott J et al. (2010) A calpain inhibitor enhances the survival of Schwann cells in vitro and after transplantation into the injured spinal cord. J Neurotrauma 27:1685-95
Fortun, Jenny; Hill, Caitlin E; Bunge, Mary Bartlett (2009) Combinatorial strategies with Schwann cell transplantation to improve repair of the injured spinal cord. Neurosci Lett 456:124-32
Talbott, Jason F; Cao, Qilin; Bertram, James et al. (2007) CNTF promotes the survival and differentiation of adult spinal cord-derived oligodendrocyte precursor cells in vitro but fails to promote remyelination in vivo. Exp Neurol 204:485-9
Golden, Kevin L; Pearse, Damien D; Blits, Bas et al. (2007) Transduced Schwann cells promote axon growth and myelination after spinal cord injury. Exp Neurol 207:203-17
Davis, Angela R; Lotocki, George; Marcillo, Alex E et al. (2007) FasL, Fas, and death-inducing signaling complex (DISC) proteins are recruited to membrane rafts after spinal cord injury. J Neurotrauma 24:823-34

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