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.
Key Findings
- 1SCI triggers diverse glial activation and cellular recruitment with complex downstream effects on neuronal function.
- 2The glial scar is important for neurotrophin production, debris clearance, blood brain barrier repair, and toxic species sequestration to the injury site.
- 3Macrophages not only can increase axon regeneration and neuronal function but can also exacerbate tissue destruction
Research Summary
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
- 1Data is limited regarding SCI scar formation in humans.
- 2Conflicting reports suggest that the prominence of the astrocytic glial scar varies between species with less astrocytosis in humans.
- 3The cellular sources and extracellular components of the glial and fibrotic scars are still being identified.