To improve recovery for individuals with SCI, gains in design and implementation of rehabilitation interventions are needed. Identifying cellular and molecular factors that impede the benefits of exercise training is an important first step. Understanding how these factors impact when rehabilitation should be initiated is also unknown. Therefore, using experimental SCI models, this proposal will explore the role of inflammation in spinal cord regions well-away from the SCI where movement is organized. The optimal window for skill training may be defined by these inflammatory mechanisms (Aim 1). We will use downhill treadmill training as it is more challenging than standard flat treadmill training. By initiating downhill training at different stages of inflammation, we will measure which stage training restores more locomotor recovery. Additionally, we will determine if activity-based training drives myelin changes along spared axons and improves function (Aim 2). These innovative studies use new transgenic technologies alongside clinically-relevant MRI approaches. Lastly, we will explore the regional differences in susceptibility to inflammation across the spinal cord (Aim 3). We may identify cord regions with high potential for training-induced recovery. Developing new types of training specifically for these pro-recovery regions may also boost functional recovery. The proposed studies have translational potential for human SCI.

Public Health Relevance

The project will identify the cellular determinants of training-induced recovery after experimental spinal cord injury. We will identify factors that influence when to begin training and whether optimal training requires myelin changes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS074882-07
Application #
9340300
Study Section
Acute Neural Injury and Epilepsy Study Section (ANIE)
Program Officer
Jakeman, Lyn B
Project Start
2011-09-01
Project End
2021-08-31
Budget Start
2017-09-01
Budget End
2018-08-31
Support Year
7
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Ohio State University
Department
Other Health Professions
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210
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Faw, Timothy D; Lerch, Jessica K; Thaxton, Tyler T et al. (2018) Unique Sensory and Motor Behavior in Thy1-GFP-M Mice before and after Spinal Cord Injury. J Neurotrauma 35:2167-2182
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Hansen, Christopher N; Faw, Timothy D; White, Susan et al. (2016) Sparing of Descending Axons Rescues Interneuron Plasticity in the Lumbar Cord to Allow Adaptive Learning After Thoracic Spinal Cord Injury. Front Neural Circuits 10:11
Hansen, Christopher N; Fisher, Lesley C; Deibert, Rochelle J et al. (2013) Elevated MMP-9 in the lumbar cord early after thoracic spinal cord injury impedes motor relearning in mice. J Neurosci 33:13101-11
Hansen, Christopher N; Linklater, William; Santiago, Raquel et al. (2012) Characterization of recovered walking patterns and motor control after contusive spinal cord injury in rats. Brain Behav 2:541-52

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