Microglia are essential for tissue contraction in wound closure after brain injury in zebrafish larvae

Abstract

Wound closure after brain injury is crucial for tissue restoration but remains poorly understood at the tissue level. We investi-gated 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. De-pleting microglia genetically or pharmacologically impairs tissue repair. At the cellular level, live imaging reveals centripetal de-formation 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.