Zebraﬁsh Spinal Cord Repair Is Accompanied by Transient Tissue Stiffening

Biophysical Journal, 2020 · DOI: https://doi.org/10.1016/j.bpj.2019.10.044 · Published: January 21, 2020

Neurology Biomechanics Regenerative Medicine & Stem Cells

Simple Explanation

Mammalian spinal cord injuries often lead to permanent paralysis due to scar tissue formation, which inhibits nerve regrowth. In contrast, zebraﬁsh can repair their spinal cords. This study investigates the mechanical properties of zebraﬁsh spinal cord tissue during this repair process. The researchers used atomic force microscopy to measure the stiffness of zebraﬁsh spinal cord tissue before and after injury. They found that the tissue stiffens during regeneration, challenging the idea that soft tissue is necessary for nerve regrowth. This research suggests that the mechanical environment plays a role in successful spinal cord repair in zebraﬁsh and that increasing tissue stiffness might promote nerve regrowth, contrary to what is believed about mammalian spinal cord injuries.

Study Duration

6-8 weeks

Participants

Zebraﬁsh (wild-type and transgenic)

Evidence Level

Not specified

Key Findings

1
In uninjured zebraﬁsh, gray matter regions of the spinal cord are stiffer than white matter regions.
2
Following spinal cord transection, the spinal cord tissue displays a transient increase in stiffness during regeneration, temporarily eliminating the mechanical difference between gray and white matter.
3
Tissue stiffness correlates variably with cell number density, oligodendrocyte interconnectivity, axonal orientation, and vascularization.

Research Summary

This study investigates the mechanical properties of the adult zebraﬁsh spinal cord during regeneration after complete spinal cord transection using atomic force microscopy. The researchers mapped the spatiotemporal changes in tissue stiffness and correlated them with cellular events. The key findings reveal that gray matter is stiffer than white matter in uninjured zebraﬁsh spinal cords. After injury, the spinal cord tissue stiffens transiently during regeneration, obliterating the mechanical difference between gray and white matter before returning to baseline values. The study challenges the common belief that scar tissue, a soft mechanical barrier, prevents axonal regrowth, suggesting that increased tissue stiffness may facilitate neuronal regeneration in zebraﬁsh. This research provides a foundation for future studies exploring the role of mechanosensing in spinal cord repair.

Practical Implications

Mechanosensing in Spinal Cord Repair

The findings provide a tissue mechanical basis for future studies into the role of mechanosensing in spinal cord repair.

Challenging the Role of Scar Tissue

The study challenges the commonly held belief that scar tissue after SCI provides a mechanical barrier to axonal regrowth.

Target Identification for Therapy

This article further starts to identify the key determinants of zebraﬁsh spinal cord mechanical properties as potential future targets to test the role of mechanosensing in successful spinal cord repair.

Study Limitations

1
The study approximates tissue as a purely elastic solid and does not account for viscous material properties.
2
The zebrafish spinal cord is significantly smaller in diameter than its murine counterpart, which aggravates precise vibratome sectioning along coronal or sagittal planes.
3
Mechanical properties of the spinal cord present in vivo could be altered due to sample preparation.

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