Recent progress has been made 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 relevance of this work to injured primate systems remains to be established. Differences in neural anatomy and function, and inter-species differences in immune and inflammatory responses to injury, raise questions regarding the simple translation of findings from rodents to primates. In the last 4 years, our consortium has established a reliable and practical model of SCI in primates, and has tested potential treatments in this model. We have found both similarities and differences in the anatomy and functional properties of intact and lesioned rodent and primate spinal cords. Further, we have preliminary evidence that plasticity can be augmented after primate SCI, leading to improved functional outcomes. The renewal of this program will build upon these findings, aiming to contribute both mechanistic and empirical knowledge leading to the development of therapeutic strategies for promoting recoveryfrom primate SCI. This project brings together research groups in a collaborative effort to advance the understanding and treatment of SCI in the following aims over the next 5years:
Specific Aim 1 : Determine Mechanisms Underlying Spontaneous RecoveryAfter Acute C5-6 Hemisection Lesions in Primates: Anatomical, Electrophysiological and Functional Studies.
Specific Aim 2 : Determine Whether BDNF Delivery Into and Below a C5-6 Hemisection Lesion Will Promote Axonal Sprouting or Regeneration, and Functional Recovery.
Specific Aim 3 : Determine Whether BDNF Delivery Into and Below a C5-6 Hemisection Lesion, + cAMP Augmentation, Will PromoteAxonal Sprouting or Regeneration, and FunctionalRecovery.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS042291-08
Application #
7575099
Study Section
Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)
Program Officer
Kleitman, Naomi
Project Start
2001-09-01
Project End
2011-02-28
Budget Start
2009-03-01
Budget End
2010-02-28
Support Year
8
Fiscal Year
2009
Total Cost
$950,449
Indirect Cost
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
Rosenzweig, Ephron S; Brock, John H; Lu, Paul et al. (2018) Restorative effects of human neural stem cell grafts on the primate spinal cord. Nat Med 24:484-490
Dulin, Jennifer N; Adler, Andrew F; Kumamaru, Hiromi et al. (2018) Injured adult motor and sensory axons regenerate into appropriate organotypic domains of neural progenitor grafts. Nat Commun 9:84
Kumamaru, Hiromi; Lu, Paul; Rosenzweig, Ephron S et al. (2018) Activation of Intrinsic Growth State Enhances Host Axonal Regeneration into Neural Progenitor Cell Grafts. Stem Cell Reports 11:861-868
Brock, J H; Rosenzweig, E S; Yang, H et al. (2018) Enhanced axonal transport: A novel form of ""plasticity"" after primate and rodent spinal cord injury. Exp Neurol 301:59-69
Patel, Akash; Li, Zhongzhi; Canete, Philip et al. (2018) AxonTracer: a novel ImageJ plugin for automated quantification of axon regeneration in spinal cord tissue. BMC Neurosci 19:8
Hunt, Matthew; Lu, Paul; Tuszynski, Mark H (2017) Myelination of axons emerging from neural progenitor grafts after spinal cord injury. Exp Neurol 296:69-73
Sparrey, Carolyn J; Salegio, Ernesto A; Camisa, William et al. (2016) Mechanical Design and Analysis of a Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates. J Neurotrauma 33:1136-49
Kadoya, Ken; Lu, Paul; Nguyen, Kenny et al. (2016) Spinal cord reconstitution with homologous neural grafts enables robust corticospinal regeneration. Nat Med 22:479-87
Lee-Kubli, Corinne A; Ingves, Martin; Henry, Kenneth W et al. (2016) Analysis of the behavioral, cellular and molecular characteristics of pain in severe rodent spinal cord injury. Exp Neurol 278:91-104
Salegio, Ernesto A; Bresnahan, Jacqueline C; Sparrey, Carolyn J et al. (2016) A Unilateral Cervical Spinal Cord Contusion Injury Model in Non-Human Primates (Macaca mulatta). J Neurotrauma 33:439-59

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