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 #
5R01NS074882-09
Application #
9763664
Study Section
Acute Neural Injury and Epilepsy Study Section (ANIE)
Program Officer
Bambrick, Linda Louise
Project Start
2011-09-01
Project End
2021-08-31
Budget Start
2019-09-01
Budget End
2020-08-31
Support Year
9
Fiscal Year
2019
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
Norden, Diana M; Faw, Timothy D; McKim, Daniel B et al. (2018) Bone Marrow-Derived Monocytes Drive the Inflammatory Microenvironment in Local and Remote Regions after Thoracic Spinal Cord Injury. J Neurotrauma :
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
Moore, Sarah A; Granger, Nicolas; Olby, Natasha J et al. (2017) Targeting Translational Successes through CANSORT-SCI: Using Pet Dogs To Identify Effective Treatments for Spinal Cord Injury. J Neurotrauma 34:2007-2018
Basso, D Michele; Lang, Catherine E (2017) Consideration of Dose and Timing When Applying Interventions After Stroke and Spinal Cord Injury. J Neurol Phys Ther 41 Suppl 3:S24-S31
Field-Fote, Edelle C; Yang, Jaynie F; Basso, D Michele et al. (2017) Supraspinal Control Predicts Locomotor Function and Forecasts Responsiveness to Training after Spinal Cord Injury. J Neurotrauma 34:1813-1825
Hansen, Christopher N; Norden, Diana M; Faw, Timothy D et al. (2016) Lumbar Myeloid Cell Trafficking into Locomotor Networks after Thoracic Spinal Cord Injury. Exp Neurol 282:86-98
Song, Rachel B; Basso, D Michele; da Costa, Ronaldo C et al. (2016) Adaptation of the Basso-Beattie-Bresnahan locomotor rating scale for use in a clinical model of spinal cord injury in dogs. J Neurosci Methods 268:117-24
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

Showing the most recent 10 out of 11 publications