Wound closure after brain injury relies on force generation by microglia in zebrafish

Abstract

Wound closure after a brain injury is critical for tissue restoration but this process is still not well characterised at the tissue level. We use live observation of wound closure in larval zebrafish after inflicting a stab wound to the brain. We demonstrate that the wound closes in the first 24 hours after injury by global tissue contraction. Microglia accumulation at the point of tissue convergence precedes wound closure and computational modelling of this process indicates that physical traction by microglia could lead to wound closure. Indeed, genetically or pharmacologically depleting microglia leads to defective tissue repair. Live observations indicate centripetal deformation of astrocytic processes contacted by migrating microglia. Severing such contacts leads to retraction of cellular processes, indicating tension. Weakening tension by disrupting the F-actin stabilising gene lcp1 in microglial cells, leads to failure of wound closure. Therefore, we propose a previously unidentified mechanism of brain repair in which microglia has an essential role in contracting spared tissue. Understanding the mechanical role of microglia will support advances in traumatic brain injury therapies Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=191 HEIGHT=200 SRC="FIGDIR/small/597300v3_ufig1.gif" ALT="Figure 1"> View larger version (53K): org.highwire.dtl.DTLVardef@112aorg.highwire.dtl.DTLVardef@6712c4org.highwire.dtl.DTLVardef@101179borg.highwire.dtl.DTLVardef@b4ecb6_HPS_FORMAT_FIGEXP M_FIG C_FIG