Softening of the chronic hemi-section spinal cord injury scar parallels dysregulation of cellular and extracellular matrix content

J Mech Behav Biomed Mater, 2020 · DOI: 10.1016/j.jmbbm.2020.103953 · Published: October 1, 2020

Simple Explanation

This study investigated the stiffness of spinal cord scar tissue after injury, focusing on the long-term (chronic) phase. The researchers measured the Young’s modulus, a measure of stiffness, of the scar tissue and analyzed its composition. They found that the chronic scar tissue was softer (had a lower Young’s modulus) than healthy spinal cord tissue. This softening was associated with changes in the cells and the extracellular matrix (ECM) that make up the scar. Specifically, the scar contained fewer normal brain/spinal cord cells, disorganized cell arrangement, and altered levels of key ECM components. These changes in the scar's structure and composition likely contribute to its reduced stiffness.

Study Duration

18 weeks

Participants

Adult rats (10-wk old; female; ~200 g weight; Fisher 344, Envigo)

Evidence Level

Not specified

Key Findings

1
The chronic spinal cord injury scar has decreased Young’s modulus compared to naïve tissue.
2
The chronic scar contains cystic cavities and dense nuclei packing, indicating tissue disorganization.
3
The chronic scar exhibits dysregulation of CNS cell types (astrocytes, oligodendrocytes, neurons) and ECM components (sulfated proteoglycans, hyaluronic acid).

Research Summary

This study demonstrates that chronic spinal cord glial scars possess decreased Young’s modulus that propagates outward from the injury core. The most significant features of the chronic scar included cystic cavities, downregulation of prevalent CNS cells, dense nuclei packing, and dysregulation of GAGs, each likely contributing to scar mechanics by altering elasticity. The results presented in this paper could lay the foundation for understanding chronic glial scar softening and provide untapped potential for future targeted therapies through GAG modulation to influence scar stiffness to match naïve tissue and support regeneration.

Practical Implications

Therapeutic targets

The dysregulation of ECM components like sulfated proteoglycans and hyaluronic acid suggests potential therapeutic targets for modulating scar stiffness and promoting regeneration.

AFM Methodology

The study highlights the importance of considering injury type, sample preparation, and AFM parameters when measuring the mechanical properties of spinal cord tissue.

Comprehensive approach to scar treatment

The findings suggest that a comprehensive approach to scar treatment should target both the chemical and mechanical barriers to regeneration, potentially through the delivery or degradation of ECM components.

Study Limitations

1
The work outlined herein specifically represents properties of a chronic hemi-section scar, which may or may not translate to other injury models and time points.
2
Measures of mechanical properties are directly related to fresh tissue sections and AFM methodologies which did not reveal information on viscous properties and likely do not directly reflect other stiffness properties such as complex modulus and tensile properties.
3
Additionally, the Hertz model makes assumptions that may or may not hold in the spinal cord injury environment.

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