Spinal cord injury (SCI) results in formation of scar tissue that plays multiple pathophysiological roles including promoting wound healing and inhibiting axon regeneration. This scar is comprised of excess deposition of extracellular matrix (ECM) molecules in both rodents and humans. In vitro assays have implicated fibroblasts as a major source of inhibitory ECM molecules, but whether this also true in vivo is not clear. While the meninges were thought to be the primary source of fibroblasts after SCI, recent evidence indicates that the perivascular niche could be an alternative source of the scar tissue. The overall goal of this proposal is to determine the translational profile of perivascular fibroblasts during scar formation after contusive SCI. By combining cell-specific mRNA isolation with Next Generation sequencing, our studies will provide a blue-print for understanding the role of perivascular fibroblasts in fibrotic scar formation after SCI.

Public Health Relevance

Patients with spinal cord injury (SCI) suffer from permanent disabilities but have limited treatment and therapeutic options. A hallmark of SCI is the formation of scar tissue that develops at the injury site. This scar tissue is thought to be important in man aspects of SCI pathophysiology including promoting wound healing and inhibiting axon regeneration. Fibroblasts have been implicated as a major component of this scar tissue, but there have been limited animal studies directly addressing this issue. We will combine cell-specific mRNA isolation with Next Generation sequencing to determine the translational profile of fibroblasts, which will provide a road-map for targeting these cells to promote functional recovery after SCI.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21NS082835-01
Application #
8489438
Study Section
Clinical Neuroplasticity and Neurotransmitters Study Section (CNNT)
Program Officer
Jakeman, Lyn B
Project Start
2013-02-01
Project End
2015-01-31
Budget Start
2013-02-01
Budget End
2014-01-31
Support Year
1
Fiscal Year
2013
Total Cost
$191,667
Indirect Cost
$66,667
Name
University of Miami School of Medicine
Department
None
Type
Organized Research Units
DUNS #
052780918
City
Coral Gables
State
FL
Country
United States
Zip Code
33146
Lee, Do-Hun; Lee, Jae K (2013) Animal models of axon regeneration after spinal cord injury. Neurosci Bull 29:436-44
Soderblom, Cynthia; Luo, Xueting; Blumenthal, Ezra et al. (2013) Perivascular fibroblasts form the fibrotic scar after contusive spinal cord injury. J Neurosci 33:13882-7