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

Neurotherapeutics, 2018 · DOI: https://doi.org/10.1007/s13311-018-0631-6 · Published: May 1, 2018

Simple Explanation

Following spinal cord injury (SCI), the body initiates a secondary cascade of vascular, inflammatory, and biochemical events that further disrupt neuronal function. These events activate glial cells, including astrocytes, fibroblasts, pericytes, Schwann cells, and microglia, leading to endogenous pathological and reparative processes in the injured central nervous system (CNS). Therapeutic strategies aim to replace, dampen, or alter their activity to modulate SCI scarring and inflammation and improve injury outcomes.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Level 5, Review

Key Findings

1
SCI triggers diverse glial activation and cellular recruitment with complex downstream effects on neuronal function.
2
The glial scar is important for neurotrophin production, debris clearance, blood brain barrier repair, and toxic species sequestration to the injury site.
3
Macrophages not only can increase axon regeneration and neuronal function but can also exacerbate tissue destruction

Research Summary

The review discusses the role of glial and inflammatory cells after SCI and therapeutic strategies targeting these cells to modulate scarring and inflammation. SCI activates resident astrocytes and recruits fibroblasts and Schwann cells, leading to glial and fibrotic scars in the injured spinal cord. Inflammation following SCI involves DAMPs engaging PRRs, activating astrocytes and microglia, and recruiting neutrophils and macrophages.

Practical Implications

Targeting CSPGs

Breaking down inhibitory extracellular matrix molecules like CSPGs with enzymes such as chondroitinase ABC facilitates axon regeneration and functional recovery.

Astrocyte Transplantation

Transplanting astrocyte stem cells can suppress scar formation and promote a permissive environment for axon growth.

Immunomodulation

Immunomodulatory approaches are being developed to potentiate reparative microglia and macrophage activation within the injured spinal cord.

Study Limitations

1
Data is limited regarding SCI scar formation in humans.
2
Conflicting reports suggest that the prominence of the astrocytic glial scar varies between species with less astrocytosis in humans.
3
The cellular sources and extracellular components of the glial and fibrotic scars are still being identified.

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