Clodronate liposome alleviates functional regeneration after peripheral nerve injury via depleting macrophages
Objective To investigate the role of macrophage depletion in functional regeneration after peripheral nerve injury.Methods Adult mice in the experimental group were intraperitoneally injected with the clodronate liposome to exhaust the macrophages and then were subjected a sciatic nerve crush injury model.The mice in the control group were administrated with the control liposome to replace the clodronate.Seven days post injury(dpi),immunofluorescence staining was performed to illustrate the F4/80 positive macrophages and the GAP43 positive regenerating axons.At 28 dpi,immunofluorescence staining was used to detect the F4/80 positive macrophages,behavior tests and neuroelectrophysiology were conducted to assay the motor function and nerve conduction.The wet weight of gastrocnemius muscle and their myofiber's size were measured to reflex the myoatrophy in the target muscles.Results The macrophages in the injured nerves were exhausted more than 70%at both 7 dpi and 28 dpi,and GAP43-positive regenerating axons in length at 7dpi were less and shorter in the experimental group than those of the control group.At 28 dpi,compared with the control group,the motor ability and nerve conduction intensity were significantly decreased,the latency of nerve conduction was prolonged,and the wet weight ratio and myofiber size were significantly reduced in the experimental group.Conclusions The clodronate liposome can alleviate the functional regeneration after peripheral nerve injury through exhausting macrophages.