This project will study how oligodendrocyte progenitor cells (OPCs) are regulated after spinal cord injury (SCI) in mice. OPCs can differentiate into remyelinating oligodendrocytes (OLs) in the adult CNS, but what signals promote this transformation are unclear in the setting of adult CNS trauma. Most studies of OPC function and myelination use chemical demyelination or neonatal cell culture models, which do not mimic the in vivo environment of the contused adult spinal cord. Thus, this project is relevant to the NIH mission since it will encompass basic science studies to discern mechanisms of spontaneous OL regeneration and myelin repair after SCI. Experiments will use a clinically relevant model of spinal contusion to evaluate mechanisms regulating OPC survival, proliferation and differentiation into new OLs after SCI. Without myelin, the ability of spared or regenerating axons to conduct action potentials will be severely hampered or completely blocked. We will use reporter mice and Cre-Lox systems to inhibit glutamate release from axons or specific intracellular signaling molecules to determine if these mechanisms regulate OPC functions after SCI. We will also use a novel model to induce demyelination after SCI to determine if and when OPC repair is greatest or when it is impaired, as our new pilot data suggest it may be impaired over time post-injury. If successful, this project will provide novel insight into how OPCs and myelination are regulated in the adult injured nervous system and may provide new therapeutic targets to improve functional recovery from SCI by enhancing both axon myelination.

Public Health Relevance

This project will study how oligodendrocyte progenitor cells responses are regulated after spinal cord injury. These cells produce myelinating oligodendrocytes after injury, which are needed for proper nerve signaling. If axons are spared or induced to grow after injury but lose their myelin, their function will be sub-optimal. Therefore, we will study mechanisms of post-injury myelination with the long-term goal of enhancing functional recovery from spinal cord injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS100522-03
Application #
9938704
Study Section
Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)
Program Officer
Bambrick, Linda Louise
Project Start
2018-06-01
Project End
2023-05-31
Budget Start
2020-06-01
Budget End
2021-05-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Ohio State University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210