This is a collaboration between experts at UCSD, UCLA, UCSF, UC Irvine, and UC Davis to examine plasticity and regeneration in the non-human primate spinal cord. Our goal is to enhance knowledge and translational relevance of research on spinal cord injury (SCI). Given findings of the last 5 years in this model, we focus this renewal on efforts to better understand and amplify the endogenous plasticity revealed in the primate system, and to test the translation of leading potential treatments discovered in non-primate models.
Aim 1 : Examine Electrophysiological and Anatomical Mechanisms Underlying Spontaneous Forelimb Functional Improvement After Primate SCI. Like humans, monkeys exhibit spontaneous improvement (but not full recovery) after C7 hemisection, and we have identified a remarkable degree of spontaneous sprouting of the primate corticospinal projection in association with this functional improvement.
Aim 1 will examine the time course of molecular, electrophysiological and systems-level (both corticospinal and non-corticospinal) mechanisms associated with behavioral improvement.
Aims 2 and 3: Test Candidate Therapies for Promoting Recovery The primate model of SCI is important not only for testing the efficacy of therapies discovered in rodents, but also for developing methods to deliver potential treatments to the larger primate system. We have tested several therapies in the last period of this grant, and plan to focus on new, promising approaches in the current grant period that target enhancement of plasticity and recovery. We will use the same techniques as in Aim 1 to examine the functional, electrophysiological, and anatomical consequences of the following:
Aim 2 : Chronic, Intermittent Stimulation with Cortically-Implanted Electrodes to Drive Plasticity of Spared Corticospinal Projections and Intraspinal Circuits.
Aim 3 : Chase Treatment after SCI.

Public Health Relevance

This research program will develop and test promising therapies for spinal cord injury in an animal model that could most closely predict human benefit. This is a collaborative endeavor between five research groups working closely together to accelerate discovery of therapies for human nervous system injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS042291-13
Application #
8640211
Study Section
Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)
Program Officer
Jakeman, Lyn B
Project Start
2011-08-15
Project End
2016-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
13
Fiscal Year
2014
Total Cost
$1,116,757
Indirect Cost
$142,743
Name
University of California San Diego
Department
Neurosciences
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Nielson, Jessica L; Haefeli, Jenny; Salegio, Ernesto A et al. (2015) Leveraging biomedical informatics for assessing plasticity and repair in primate spinal cord injury. Brain Res 1619:124-38
Koffler, Jacob; Samara, Ramsey F; Rosenzweig, Ephron S (2014) Using templated agarose scaffolds to promote axon regeneration through sites of spinal cord injury. Methods Mol Biol 1162:157-65
Nielson, Jessica L; Guandique, Cristian F; Liu, Aiwen W et al. (2014) Development of a database for translational spinal cord injury research. J Neurotrauma 31:1789-99
Do, Jiun L; Bonni, Azad; Tuszynski, Mark H (2013) SnoN facilitates axonal regeneration after spinal cord injury. PLoS One 8:e71906
Nout, Yvette S; Ferguson, Adam R; Strand, Sarah C et al. (2012) Methods for functional assessment after C7 spinal cord hemisection in the rhesus monkey. Neurorehabil Neural Repair 26:556-69
Nout, Yvette S; Rosenzweig, Ephron S; Brock, John H et al. (2012) Animal models of neurologic disorders: a nonhuman primate model of spinal cord injury. Neurotherapeutics 9:380-92
Jindrich, Devin L; Courtine, Gregoire; Liu, James J et al. (2011) Unconstrained three-dimensional reaching in rhesus monkeys. Exp Brain Res 209:35-50
Brock, John H; Rosenzweig, Ephron S; Blesch, Armin et al. (2010) Local and remote growth factor effects after primate spinal cord injury. J Neurosci 30:9728-37
Edgerton, V Reggie; Roy, Roland R (2009) Activity-dependent plasticity of spinal locomotion: implications for sensory processing. Exerc Sport Sci Rev 37:171-8
Rosenzweig, Ephron S; Brock, John H; Culbertson, Maya D et al. (2009) Extensive spinal decussation and bilateral termination of cervical corticospinal projections in rhesus monkeys. J Comp Neurol 513:151-63

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