Our long-term goal is to develop treatments for acute and chronic spinal cord injury (SCI) that can be translated into the clinic. Therapeutic interventions, such as transplantation and exercise (EX), lead to reorganization of the spinal cord, as shown by anatomical, physiological and behavioral assays. Our Projects will address transplant (TP)-mediated effects on recovery of function and the reliance of recovery on actions at local and/or distant sites. Project 1 will focus on the benefits offered by transplantation of neural restricted precursor cells (neuronal and glial) after adult rat SCI. Basic mechanisms by which stem cell IPs promote neuroprotection, long distance axonal growth, relay information across a lesion and support recovery of function will be explored. Project 2 will use spinalized cats to test whether behavioral recovery attained with neurotrophin-producing IPs results from axonal regeneration or local trophic effects. Experiments will test for recovery of function when transplantation is delayed after injury and will define sensory and motor influences on reorganization of lumbar locomotor circuits (i.e. CPG) after training or transplantation. Project 3 will use spinalized rats to address mechanisms of IP- and EX-mediated reorganization of spinal cord circuitry. Whether activity-dependent plasticity creates an environment more conducive to axonal regeneration and if plasticity of neuromuscular junctions relates to improved functional capabilities will be examined. The Administration Core will organize weekly meetings of PPG participants, prepare progress reports and maintain the entire PPG budget. The Behavior and Biomechanics Core will conduct established and novel behavioral assessments of SCI animals to specify the effects of lesions and treatments and to provide insights into recovery mechanisms. The Cell and Molecular Biology Core will provide stem cells and modified fibroblasts for transplantation and assist with PCR and protein assays. The Histology Core will prepare tissue sections for tract tracing and immunocytochemical reactions and perform image analysis of TP-mediated axonal regeneration and sprouting. The Surgery Core will assist with preparation of SCI animals and transplantation procedures. Our strategy is to employ multiple injury models and combinations of treatments to promote repair and to understand mechanisms of functional recovery. This program has direct relevance to the design and implementation of future treatment programs for SCI.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS055976-04
Application #
7796582
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Kleitman, Naomi
Project Start
2007-06-15
Project End
2012-03-31
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
4
Fiscal Year
2010
Total Cost
$1,176,947
Indirect Cost
Name
Drexel University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
002604817
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Spruance, Victoria M; Zholudeva, Lyandysha V; Hormigo, Kristiina M et al. (2018) Integration of Transplanted Neural Precursors with the Injured Cervical Spinal Cord. J Neurotrauma 35:1781-1799
Zholudeva, Lyandysha V; Qiang, Liang; Marchenko, Vitaliy et al. (2018) The Neuroplastic and Therapeutic Potential of Spinal Interneurons in the Injured Spinal Cord. Trends Neurosci 41:625-639
Bezdudnaya, Tatiana; Hormigo, Kristiina M; Marchenko, Vitaliy et al. (2018) Spontaneous respiratory plasticity following unilateral high cervical spinal cord injury in behaving rats. Exp Neurol 305:56-65
Kar, Amar N; Lee, Seung Joon; Twiss, Jeffery L (2018) Expanding Axonal Transcriptome Brings New Functions for Axonally Synthesized Proteins in Health and Disease. Neuroscientist 24:111-129
Jin, Ying; Shumsky, Jed S; Fischer, Itzhak (2018) Axonal regeneration of different tracts following transplants of human glial restricted progenitors into the injured spinal cord in rats. Brain Res 1686:101-112
Zholudeva, Lyandysha V; Iyer, Nisha; Qiang, Liang et al. (2018) Transplantation of Neural Progenitors and V2a Interneurons after Spinal Cord Injury. J Neurotrauma 35:2883-2903
Chhaya, Soha J; Quiros-Molina, Daniel; Tamashiro-Orrego, Alessandra D et al. (2018) Exercise-Induced Changes to the Macrophage Response in the Dorsal Root Ganglia Prevent Neuropathic Pain after Spinal Cord Injury. J Neurotrauma :
Sahoo, Pabitra K; Smith, Deanna S; Perrone-Bizzozero, Nora et al. (2018) Axonal mRNA transport and translation at a glance. J Cell Sci 131:
Dimiskovski, Marko; Scheinfield, Richard; Higgin, Dwight et al. (2017) Characterization and validation of a split belt treadmill for measuring hindlimb ground-reaction forces in able-bodied and spinalized felines. J Neurosci Methods 278:65-75
Krupka, Alexander J; Fischer, Itzhak; Lemay, Michel A (2017) Transplants of Neurotrophin-Producing Autologous Fibroblasts Promote Recovery of Treadmill Stepping in the Acute, Sub-Chronic, and Chronic Spinal Cat. J Neurotrauma 34:1858-1872

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