Delayed post‐injury administration of C 5a improves regeneration and functional recovery after spinal cord injury in mice

Summary The activation of a complement system can aggravate the secondary injury after spinal cord injury ( SCI ). However, it was reported recently that the activation of a complement could have both a secondary injury and a neuroprotective effect, in which C 5a is the most important factor, but there is no direct evidence for this dual effect of C 5a after SCI . In order to investigate the potential neuroprotective effect of C 5a after SCI , in this study ectogenic C 5a was injected intraperitoneally before/after SCI   in vivo , or administrated to mechanically injured neurones in vitro ; following this, neurone apoptosis, neurite outgrowth, axonal regeneration and functional recovery were investigated. The in‐vivo experiments indicated that, following treatment with C 5a 24 h before or immediately after injury, locomotor function was impaired significantly. However, when treatment with C 5a took place 24 h after injury, locomotor function improved significantly. In‐vitro experiments indicated that a certain concentration of C 5a (50–100  nM ) could inhibit caspase‐3‐mediated neurone apoptosis by binding to its receptor CD 88, and that it could even promote the neurite outgrowth of uninjured neurones. In conclusion, delayed post‐injury administration of C 5a within a certain concentration could exert its neuroprotective effect through inhibiting caspase‐3‐mediated neurone apoptosis and promoting neurite outgrowth of uninjured neurones as well. These data suggest that C 5a may have opposite functions in a time‐ and concentration‐dependent manner after SCI . The dual roles of C 5a have to be taken into account when measures are taken to inhibit complement activation in order to promote regeneration after SCI .