Fibrotic Scar After Spinal Cord Injury: Crosstalk With Other Cells, Cellular Origin, Function, and Mechanism

Frontiers in Cellular Neuroscience, 2021 · DOI: 10.3389/fncel.2021.720938 · Published: August 26, 2021

Spinal Cord Injury Genetics Research Methodology & Design

Simple Explanation

Spinal cord injury (SCI) often leads to permanent loss of movement and sensation due to the failure of nerve fibers (axons) to regenerate. Scar tissue, particularly fibrotic scar, is a major obstacle to this regeneration. This review focuses on fibrotic scar tissue, exploring how it forms, interacts with other cells in the injured area, and its role in preventing axon regeneration. Understanding these aspects is crucial for developing new treatments for SCI. The review also discusses the cellular origins of fibrotic scars, specifically how certain cells transform into scar-forming cells after SCI. This knowledge can help in devising targeted therapies to prevent or modify scar formation.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Fibrotic scar tissue, composed of fibroblasts and excess extracellular matrix, forms after SCI and inhibits axonal regeneration.
2
Fibrotic scar interacts with astrocytes, macrophages, and microglia in the injured spinal cord, creating a complex network that influences scar formation and axonal regeneration.
3
Pericytes, specifically type A pericytes, are identified as the primary source of fibroblasts that form the fibrotic scar after SCI.

Research Summary

This review summarizes the current understanding of fibrotic scar formation after spinal cord injury (SCI), its cellular origins, and its interactions with other cells in the injured area. It highlights the dual role of fibrotic scar, contributing to tissue integrity and limiting inflammation in the early phase of SCI, while inhibiting axonal regeneration in the chronic phase. The review also discusses potential therapeutic targets and strategies for modulating fibrotic scar formation to promote axonal regeneration and functional recovery after SCI.

Practical Implications

Targeted Therapies

The identification of pericytes as the primary source of fibrotic scar-forming fibroblasts allows for the development of targeted therapies to prevent or modulate scar formation.

Combination Therapies

Understanding the crosstalk between fibrotic scar and other cells (astrocytes, macrophages, microglia) can lead to the development of combination therapies that address multiple aspects of scar formation and inflammation.

Phased Interventions

Recognizing the dual role of fibrotic scar suggests that interventions should be tailored to the specific phase of SCI, promoting scar formation early on while inhibiting it later to maximize axonal regeneration.

Study Limitations

1
Differences in fibrotic scar formation between species (mice vs. rats) may limit the direct translation of findings from animal models to human SCI.
2
The role of inflammatory cells other than macrophages in fibrotic scar formation requires further investigation.
3
Specific intracellular signaling pathways involved in the crosstalk between fibroblasts and other cells need further exploration.

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