Microglia Stimulate Zebrafish Brain Repair Via a Tumor Necrosis Factor-<i>α</i>-Initiated Inflammatory Cascade

The study demonstrated that microglia played a crucial role in zebrafish brain repair by regulating the inflammatory response necessary for regeneration. Researchers used various methods to ablate microglia, including liposomal clodronate and csf1r inhibition, and observed that the absence of microglia inhibited neurogenesis and regeneration. Specifically, microglial suppression affected cell proliferation during the progenitor cell amplification stage. The study found that microglia influenced phospho-stat3 and ß-catenin signaling through tumor necrosis factor-α regulation, and activating these pathways could rescue neurogenesis defects. Additionally, the absence of microglia led to neutrophil accumulation, which impeded inflammation resolution, and macrophages alone were insufficient for regeneration. These findings highlighted the importance of microglia and inflammatory signaling in zebrafish brain repair, suggesting potential strategies for enhancing mammalian brain repair.