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Exp Neurol. 2014 Aug;258:24-34. doi: 10.1016/j.expneurol.2013.11.020.

Extracellular matrix regulation of inflammation in the healthy and injured spinal cord.

Author information

1
Center for Brain and Spinal Cord Repair, Department of Neuroscience, College of Medicine, The Ohio State University, 670 Biomedical Research Tower, 460 West 12th Ave., Columbus, OH 43210, USA. Electronic address: andrew.gaudet@osumc.edu.
2
Center for Brain and Spinal Cord Repair, Department of Neuroscience, College of Medicine, The Ohio State University, 670 Biomedical Research Tower, 460 West 12th Ave., Columbus, OH 43210, USA. Electronic address: phillip.popovich@osumc.edu.

Abstract

Throughout the body, the extracellular matrix (ECM) provides structure and organization to tissues and also helps regulate cell migration and intercellular communication. In the injured spinal cord (or brain), changes in the composition and structure of the ECM undoubtedly contribute to regeneration failure. Less appreciated is how the native and injured ECM influences intraspinal inflammation and, conversely, how neuroinflammation affects the synthesis and deposition of ECM after CNS injury. In all tissues, inflammation can be initiated and propagated by ECM disruption. Molecules of ECM newly liberated by injury or inflammation include hyaluronan fragments, tenascins, and sulfated proteoglycans. These act as "damage-associated molecular patterns" or "alarmins", i.e., endogenous proteins that trigger and subsequently amplify inflammation. Activated inflammatory cells, in turn, further damage the ECM by releasing degradative enzymes including matrix metalloproteinases (MMPs). After spinal cord injury (SCI), destabilization or alteration of the structural and chemical compositions of the ECM affects migration, communication, and survival of all cells - neural and non-neural - that are critical for spinal cord repair. By stabilizing ECM structure or modifying their ability to trigger the degradative effects of inflammation, it may be possible to create an environment that is more conducive to tissue repair and axon plasticity after SCI.

KEYWORDS:

DAMP; Hyaluronan; Immune; Neuroinflammation; Proteoglycan; TLR; Tenascin; Toll-like receptors

PMID:
25017885
PMCID:
PMC4099942
DOI:
10.1016/j.expneurol.2013.11.020
[Indexed for MEDLINE]
Free PMC Article

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