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 nerve fiber degeneration and regeneration, as well as in glial and neuronal cell responses in the central nervous system (CNS). Adult congenic mice lacking C5 (C5(-)) and the corresponding normal strain (C5(+)) were used. Macrophage recruitment as well as axonal and myelin sheath elimination were delayed from 1 to 21 days postinjury in C5(-) mice compared to the C5(+) group after sciatic nerve crush. Despite this, recovery of motor function was not delayed. In the CNS, microglial cells and astrocytes responded in the same way from 3 to 21 days after sciatic nerve injury in C5(-) and C5(+) mice, and the extent of neuron death following hypoglossal nerve avulsion was the same in both groups. These findings suggest that C5 and/or its derivatives play an important role in initiating the recruitment of macrophages to the injured nerve and, probably indirectly, in early remyelination of regenerating axons, but does not influence the longterm functional restoration or axotomy-induced nerve cell death. C5-derived molecules do not appear to participate in central glial cell responses to peripheral nerve injury. These findings elucidate new aspects on the functional role of the complement system in the peripheral nervous system following peripheral nerve injury.
Liu
L
L
Department of Neuroscience, Biomedical Center, Uppsala University, Sweden. Li.Liu@anatomi.uu.se
Lioudyno
M
M
Tao
R
R
Eriksson
P
P
Svensson
M
M
Aldskogius
H
H
D000818:Animals; D003182:Complement C5 / Q000172:deficiency*; D005154:Facial Nerve / Q000473:pathology / Q000503:physiopathology; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis; D007002:Hypoglossal Nerve / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D004676:Myelin Basic Protein / Q000032:analysis; D009409:Nerve Crush; D012016:Reference Values; D012584:Sciatic Nerve / Q000473:pathology / Q000502:physiology / Q000503:physiopathology*; D014855:Wallerian Degeneration / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*
D003182:Complement C5; D005904:Glial Fibrillary Acidic Protein; D004676:Myelin Basic Protein