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Neurotherapeutics

, Volume 15, Issue 3, pp 541–553 | Cite as

Spinal Cord Injury Scarring and Inflammation: Therapies Targeting Glial and Inflammatory Responses

  • Michael B. Orr
  • John C. Gensel
Review

Abstract

Deficits in neuronal function are a hallmark of spinal cord injury (SCI) and therapeutic efforts are often focused on central nervous system (CNS) axon regeneration. However, secondary injury responses by astrocytes, microglia, pericytes, endothelial cells, Schwann cells, fibroblasts, meningeal cells, and other glia not only potentiate SCI damage but also facilitate endogenous repair. Due to their profound impact on the progression of SCI, glial cells and modification of the glial scar are focuses of SCI therapeutic research. Within and around the glial scar, cells deposit extracellular matrix (ECM) proteins that affect axon growth such as chondroitin sulfate proteoglycans (CSPGs), laminin, collagen, and fibronectin. This dense deposition of material, i.e., the fibrotic scar, is another barrier to endogenous repair and is a target of SCI therapies. Infiltrating neutrophils and monocytes are recruited to the injury site through glial chemokine and cytokine release and subsequent upregulation of chemotactic cellular adhesion molecules and selectins on endothelial cells. These peripheral immune cells, along with endogenous microglia, drive a robust inflammatory response to injury with heterogeneous reparative and pathological properties and are targeted for therapeutic modification. Here, we review the role of glial and inflammatory cells after SCI and the therapeutic strategies that aim to replace, dampen, or alter their activity to modulate SCI scarring and inflammation and improve injury outcomes.

Key Words

Macrophage human chondroitinase ABC (chABC) azithromycin glial limitans traumatic brain injury. 

Notes

Acknowledgments

This work is supported by NIH R01 NS091582. Stipend support for MO from the Kentucky Spinal Cord and Head Injury Research Trust and the University of Kentucky College of Medicine Fellowship for Excellence in Graduate Research. The authors would like to thank Phillip Popovich and the editors, Mar Cortes, Keith Tansey, and Guillermo Garcia-Alias, for their endorsements.

Required Author Forms

Disclosure forms provided by the authors are available with the online version of this article.

Supplementary material

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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2018

Authors and Affiliations

  1. 1.Spinal Cord and Brain Injury Research Center, Department of PhysiologyUniversity of Kentucky College of MedicineLexingtonUSA

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