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Updated: Jun 10, 2025
Stab Wound Injury Model of the Adult Optic Tectum Using Zebrafish and Medaka for the Comparative Analysis of Regenerative Capacity
Published on: February 10, 2022
Microglia are essential for tissue contraction in wound closure after brain injury in zebrafish larvae
Francois El-Daher1,2, Stephen J Enos2, Louisa K Drake3
1Centre for Discovery Brain Sciences, University of Edinburgh Medical School: Biomedical Sciences, Edinburgh, UK francois.el-daher@ed.ac.uk.
Abstract:
Wound closure after brain injury is crucial for tissue restoration but remains poorly understood at the tissue level. We investigated this process using in vivo observations of larval zebrafish brain injury. Our findings show that wound closure occurs within the first 24 h through global tissue contraction, as evidenced by live-imaging and drug inhibition studies. Microglia accumulate at the wound site before closure, and computational models suggest that their physical traction could drive this process. Depleting microglia genetically or pharmacologically impairs tissue repair. At the cellular level, live imaging reveals centripetal deformation of astrocytic processes contacted by migrating microglia. Laser severing of these contacts causes rapid retraction of microglial processes and slower retraction of astrocytic processes, indicating tension. Disrupting the lcp1 gene, which encodes the F-actin-stabilising protein L-plastin, in microglia results in failed wound closure. These findings support a mechanical role of microglia in wound contraction and suggest that targeting microglial mechanics could offer new strategies for treating traumatic brain injury.
Insights
Brain injury repair involves tissue contraction driven by microglia. Targeting microglial mechanics may offer new treatments for traumatic brain injury (TBI).
Area of Science:
- Neuroscience
- Cell Biology
- Biophysics
Background:
- Wound closure is vital for brain injury recovery but poorly understood at the tissue level.
- Mechanisms driving tissue restoration after central nervous system injury require further elucidation.
Purpose of the Study:
- To investigate the in vivo mechanisms of wound closure in larval zebrafish brain injury.
- To determine the role of microglia in the mechanical process of brain tissue repair.
Main Methods:
- In vivo live-imaging of larval zebrafish brain injury.
- Drug inhibition studies and genetic depletion of microglia.
- Computational modeling and laser-based cellular contractility assays.
- Analysis of the lcp1 gene's role in microglial function.
Main Results:
- Brain wound closure occurs within 24 hours via global tissue contraction.
- Microglia accumulate at wound sites and exert physical traction, driving closure.
- Depleting microglia or disrupting L-plastin (encoded by lcp1) impairs wound repair.
- Microglia-induced tension deforms astrocytic processes at cellular contacts.
Conclusions:
- Microglia play a critical mechanical role in brain wound contraction.
- Targeting microglial mechanics presents a potential therapeutic strategy for traumatic brain injury.
