糖心TV

Abstract: Spinal cord injury leads to a massive response of innate immune cells (microglia, macrophages, neutrophils) both in non-regenerating mammals and in successfully regenerating zebrafish, but the role of these immune cells in functional spinal cord regeneration in zebrafish is unclear. We have recently established a spinal cord lesion paradigm in 3-day-old larval zebrafish. These show axonal and neuronal repair within 48 hours, with axons actively navigating a complex extracellular matrix. We use this highly accessible system to determine interactions of innate immune cells and signals in successful spinal cord repair.

Inhibiting inflammation reduces and promoting it accelerates axonal regeneration in larval  zebrafish. Similarly, regeneration of motor neurons is promoted by signals from the innate immune systems. Mutant analyses show that peripheral macrophages, but not neutrophils or microglia, are necessary for axon regeneration. Macrophage-less irf8 mutants show prolonged inflammation with elevated levels of Il-1尾 and Tnf-伪. Decreasing Il-1尾 levels or number of Il-1尾+ neutrophils rescues functional regeneration in irf8 mutants. However, during early regeneration, interference with Il-1尾 function impairs regeneration in irf8 and wildtype animals. Inhibiting Tnf-伪 does not rescue axonal growth in irf8 mutants, but impairs it in wildtype animals, indicating a pro-regenerative role of Tnf-伪

 Hence, inflammation is tightly and dynamically controlled by macrophages to promote functional spinal cord regeneration in zebrafish.