The soft mechanical signature of glial scars in the central nervous system

Nature Communications, 2017 · DOI: 10.1038/ncomms14787 · Published: March 20, 2017

Simple Explanation

Injury to the central nervous system (CNS) alters the molecular and cellular composition of neural tissue and leads to glial scarring, which inhibits the regrowth of damaged axons. Glial scars are thought to provide not only a biochemical but also a mechanical barrier to neuronal regeneration. In addition to repressive ECM molecules and other signalling molecules produced by glial scars, such as chondroitin sulphate proteoglycans (CSPGs)18, a dense meshwork of cells and ECM allegedly constitute a ‘stiff’ obstacle which neurons cannot penetrate17. Using atomic force microscopy (AFM) indentation experiments, here we show that, in contrast to all other known scars, glial scars in both the rat cortex and spinal cord are softer than healthy CNS tissue.

Study Duration

1.5 and 3 weeks

Participants

Rats

Evidence Level

Not specified

Key Findings

1
In contrast to scars in other mammalian tissues, CNS tissue signiﬁcantly softens after injury.
2
Expression levels of glial intermediate ﬁlaments (GFAP, vimentin) and extracellular matrix components (laminin, collagen IV) correlate with tissue softening.
3
The observed decrease in cortical tissue stiffness after stab injury correlated in all three investigated tissue sections with an increased expression of vimentin, GFAP, laminin and collagen IV.

Research Summary

This study measured the mechanical properties of the adult rat brain cortex and spinal cord in normal conditions and in response to two different types of traumatic injury using AFM. Healthy CNS tissue is mechanically heterogeneous; we found grey matter to be about twice as stiff as white matter in both brain and spinal cord Here we show that, similar to tissue that replaces CNS tissue after spinal cord hemisections36, neural tissue itself in both the rat brain cortex and spinal cord does not stiffen but rather becomes softer after injury.

Practical Implications

Regenerative Medicine

Providing appropriate mechanical signals in addition to permissive chemical signals should be considered in future approaches in regenerative medicine.

Neural Implant Design

Mechanical environment should be considered in the design of neural implants to ultimately facilitate functional recovery after CNS injuries.

Stem Cell Fate

The softening of mammalian CNS tissue after injury might tune the stem cell fate towards glial cell lineages, limiting axon growth.

Study Limitations

1
Greater variability between individual animals compared to cortical stab lesions, likely due to the variable amounts of tissue damage associated with this injury model and a higher level of uncertainty in determining the correct size and location of the lesion.
2
Because patterns of glial cell activation and tissue softening seemed to overlap, we investigated whether there was a direct spatial correlation between tissue softening and the expression of glial intermediate ﬁlament or ECM protein markers. To perform a precise correlation analysis, we only considered samples for which AFM and immunoﬂuorescence measurements could be done on slices of the very same plane, which restricted our analysis to three samples from 9, 21 and 22 days PI.
3
The boundaries of the lesion were determined by eye.

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