Delay Modulates the Immune Response to Nerve Repair

Effective regeneration after peripheral nerve injury requires macrophage recruitment. We investigated activation of remodeling pathways within the macrophage population when repair is delayed and identified alteration of key upstream regulators of the inflammatory response. We then targeted one of these regulators, using exogenous IL10 to manipulate the response to injury at the repair site. We demonstrate that this approach alters macrophage polarization, promotes macrophage recruitment, axon extension, neuromuscular junction formation and increases the number of regenerating motor units reaching their target. We also demonstrate that this approach can rescue the effects of delayed nerve graft. Overall design: Comparison of Delayed vs Immediate repair in sciatic nerve branches of mice 5 and 14 days after injury. Evaluated at 5 or 14 days after delayed or immediate graft repair