Hereditary absence of complement C5 in adult mice influences wallerian degeneration, but not retrograde responses, following injury to peripheral nerve

We have examined the role of complement component 5 (C5) in peripheral nerv e fiber degeneration and regeneration, as well as in glial and neuronal cel l responses in the central nervous system (CNS). Adult congenic mice lackin g C5 (C5(-)) and the corresponding normal strain (C5(+)) were used. Macroph age recruitment as well as axonal and myelin sheath elimination were delaye d from 1 to 21 days postinjury in C5(-) mice compared to the C5(+) group af ter sciatic nerve crush. Despite this, recovery of motor function was not d elayed. In the CNS, microglial cells and astrocytes responded in the same w ay from 3 to 21 days after sciatic nerve injury in C5(-) and C5(+) mice, an d the extent of neuron death following hypoglossal nerve avulsion was the s ame in both groups. These findings suggest that C5 and/or its derivatives p lay an important role in initiating the recruitment of macrophages to the i njured nerve and, probably indirectly, in early remyelination of regenerati ng axons, but does not influence the longterm functional restoration or axo tomy-induced nerve cell death. CS-derived molecules do not appear to partic ipate in central glial cell responses to peripheral nerve injury. These fin dings elucidate new aspects on the functional role of the complement system in the peripheral nervous system following peripheral nerve injury.