In the presence of danger: the extracellular matrix defensive response to central nervous system injury

Neural Regen Res, 2014 · DOI: 10.4103/1673-5374.128238 · Published: February 1, 2014

Simple Explanation

Glial cells contribute to the extracellular matrix (ECM), which enhances neurotransmission and axon propagation. After CNS trauma, glial cells change the ECM composition, creating an environment that inhibits migration of repair cells and axonal regrowth. This glial response limits the invasion of damaging cells and diffusion of toxic molecules into spared tissue regions. Current research focuses on modifying the inhibitory environment without eliminating the protective functions of glial cell activation. This article highlights structural and functional features of the normal adult CNS ECM and then focuses on the reactions of glial cells and changes in the perilesion border that occur following spinal cord or contusive brain injury.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review Article

Key Findings

1
Following CNS injury, glial cells activate and alter the ECM composition at the lesion border, creating a growth-inhibitory environment.
2
This response, while limiting damage spread, also inhibits migration of endogenous repair cells and axonal regrowth.
3
Research is focused on modifying the inhibitory perilesion microenvironment while retaining the protective functions of glial cell activation.

Research Summary

Glial cells in the central nervous system (CNS) contribute to formation of the extracellular matrix, which provides adhesive sites, signaling molecules, and a diffusion barrier to enhance efficient neurotransmission and axon potential propagation. However, after trauma such as a spinal cord injury or cortical contusion, the lesion epicenter becomes a focus of acute neuroinflammation. The activation of the surrounding glial cells leads to a dramatic change in the composition of the ECM at the edges of the lesion, creating a perilesion environment dominated by growth inhibitory molecules and restoration of the peripheral/central nervous system border. This article highlights structural and functional features of the normal adult CNS ECM and then focuses on the reactions of glial cells and changes in the perilesion border that occur following spinal cord or contusive brain injury.

Practical Implications

Targeted Therapies

Developing ECM-targeted therapies to promote axonal growth and plasticity after CNS injury.

Combination Strategies

Combining cell grafting, axon growth activation, and rehabilitation therapies with ECM modifications.

Understanding Glial Response

Further elucidating the dual roles of the glial response and ECM changes following injury to improve therapeutic approaches.

Study Limitations

1
The functional effects of ECM targeted therapies alone have been limited largely because they do not address cellular replacement or sufficiently drive the intrinsic growth potential of injured CNS neurons.
2
Sorting through the results of many different combinations and experimental models will take time.
3
The signals that induce expression of inhibitory ECM molecules at the lesion site are still being identified.

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