Journal
CELL AND TISSUE RESEARCH
Volume 387, Issue 3, Pages 319-336Publisher
SPRINGER
DOI: 10.1007/s00441-021-03477-w
Keywords
Glia; Glial scar; Glial scar formation; Spinal cord injury; Chondroitin sulfate proteoglycans; Single-cell RNA sequencing
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Funding
- NINDS [NS25713]
- Ohio Department of Higher Education-Third Frontier Program
- Brumagin-Nelson Fund
- Kaneko Family Fund
- Hong Kong Spinal Cord Injury Fund
- King's Prize Fellowship
- Medical Research Council [UKRI MR/S011110/1]
- Brotman Baty Institute
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Severe spinal cord injury leads to permanent loss of function and sensation, forming a glial/fibrotic scar. The importance of scar modulation in recovery after traumatic injury is increasingly recognized. Future therapeutic approaches should focus on scar modulation for restoring function.
Severe spinal cord injury causes permanent loss of function and sensation throughout the body. The trauma causes a multifaceted torrent of pathophysiological processes which ultimately act to form a complex structure, permanently remodeling the cellular architecture and extracellular matrix. This structure is traditionally termed the glial/fibrotic scar. Similar cellular formations occur following stroke, infection, and neurodegenerative diseases of the central nervous system (CNS) signifying their fundamental importance to preservation of function. It is increasingly recognized that the scar performs multiple roles affecting recovery following traumatic injury. Innovative research into the properties of this structure is imperative to the development of treatment strategies to recover motor function and sensation following CNS trauma. In this review, we summarize how the regeneration potential of the CNS alters across phyla and age through formation of scar-like structures. We describe how new insights from next-generation sequencing technologies have yielded a more complex portrait of the molecular mechanisms governing the astrocyte, microglial, and neuronal responses to injury and development, especially of the glial component of the scar. Finally, we discuss possible combinatorial therapeutic approaches centering on scar modulation to restore function after severe CNS injury.
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