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  4. Current Advancements in Spinal Cord Injury Research—Glial Scar Formation and Neural Regeneration

Current Advancements in Spinal Cord Injury Research—Glial Scar Formation and Neural Regeneration

Cells, 2023 · DOI: 10.3390/cells12060853 · Published: March 9, 2023

Spinal Cord InjuryRegenerative MedicineNeurology

Simple Explanation

Spinal cord injury (SCI) leads to permanent damage in the central nervous system, causing issues like axonal degeneration and scar formation. The glial scar forms to protect healthy tissue by isolating inflammation at the injury site. While the glial scar protects viable neural tissue, it also hinders regeneration. Therapeutic strategies focus on preventing scar formation, resolving the scar, transplanting cells, and reprogramming endogenous cells to promote regeneration after SCI. This review explores the cellular and molecular aspects of glial scar formation and discusses the benefits and drawbacks of different strategies aimed at promoting neural regeneration following spinal cord injury.

Study Duration
Not specified
Participants
Not specified
Evidence Level
Review

Key Findings

  • 1
    The glial scar, composed of astrocytes, fibroblasts, and microglia, forms a physicochemical barrier that isolates inflammation but also inhibits neural regeneration.
  • 2
    Therapeutic strategies to overcome the negative effects of glial scar formation include preventing scar formation, resolving developed scars, cell transplantation, and endogenous cell reprogramming.
  • 3
    Current research in therapeutic interventions are categorized as: behavioral, biological, device, drug, dietary, procedural, radiation, and combinatorial. Biological strategies include targeting scar formation, resolving the glial scar, cell transplantation, and endogenous cell reprogramming.

Research Summary

Spinal cord injury (SCI) leads to detrimental cellular processes, including axonal degeneration, neuronal loss, neuroinflammation, reactive gliosis, and scar formation. The glial scar border forms to segregate the neural lesion and isolate spreading inflammation, reactive oxygen species, and excitotoxicity at the injury epicenter to preserve surrounding healthy tissue. The glial scar border is a physicochemical barrier composed of elongated astrocytes, fibroblasts, and microglia secreting chondroitin sulfate proteoglycans, collogen, and the dense extra-cellular matrix. While this physiological response preserves viable neural tissue, it is also detrimental to regeneration. Therapeutic strategies have been developed to overcome negative outcomes associated with scar formation: the prevention of scar formation, the resolution of the developed scar, cell transplantation into the lesion, and endogenous cell reprogramming.

Practical Implications

Targeting Glial Scar Formation

Hindering glial scar formation or decreasing the aggregation of astrocytes may reduce or remove this barrier to promote regeneration.

Cell Transplantation Strategies

Transplantation of cells may be beneficial to supplement the neuronal number or recover native neurons in the injury site. Changing the local microenvironment may attenuate inhibition to allow for axonal regeneration.

Endogenous Cell Reprogramming via Gene Delivery

Gene delivery has emerged as an effective approach to promote regeneration and reduce glial scar formation via endogenous cell reprogramming in the injured spinal cord.

Study Limitations

  • 1
    Heterogeneity and complex pathophysiology of SCI
  • 2
    Few therapeutics successfully translate to clinical trials
  • 3
    Safety of viral delivery systems must be considered for clinical therapeutics

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