title: Soluble complement receptor 1 protects the peripheral nerve from early axon loss after injury.
abstract: Complement activation is a crucial early event in Wallerian degeneration. In this study we show that treatment of rats with soluble complement receptor 1 (sCR1), an inhibitor of all complement pathways, blocked both systemic and local complement activation after crush injury of the sciatic nerve. Deposition of membrane attack complex (MAC) in the nerve was inhibited, the nerve was protected from axonal and myelin breakdown at 3 days after injury, and macrophage infiltration and activation was strongly reduced. We show that both classical and alternative complement pathways are activated after acute nerve trauma. Inhibition of the classical pathway by C1 inhibitor (Cetor) diminished, but did not completely block, MAC deposition in the injured nerve, blocked myelin breakdown, inhibited macrophage infiltration, and prevented macrophage activation at 3 days after injury. However, in contrast to sCR1 treatment, early signs of axonal degradation were visible in the nerve, linking MAC deposition to axonal damage. We conclude that sCR1 protects the nerve from early axon loss after injury and propose complement inhibition as a potential therapy for the treatment of diseases in which axon loss is the main cause of disabilities.
authors: Academic Medical Center, Neurogenetics Laboratory, Meibergdreef 9, Amsterdam Zuidoost, The Netherlands.
authors: Valeria
authors: V
authors: Ramaglia
authors: Ruud
authors: R
authors: Wolterman
authors: Maryla
authors: M
authors: de Kok
authors: Miriam Ann
authors: MA
authors: Vigar
authors: Ineke
authors: I
authors: Wagenaar-Bos
authors: Rosalind Helen Mary
authors: RH
authors: King
authors: Brian Paul
authors: BP
authors: Morgan
authors: Frank
authors: F
authors: Baas
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000473:pathology*; D003167:Complement Activation / Q000187:drug effects; D003170:Complement Pathway, Alternative / Q000187:drug effects; D006801:Humans; D008262:Macrophage Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000473:pathology; D008297:Male; D009186:Myelin Sheath / Q000378:metabolism; D009409:Nerve Crush; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010525:Peripheral Nerves / Q000187:drug effects* / Q000473:pathology* / Q000648:ultrastructure; D051381:Rats; D011951:Receptors, Complement / Q000378:metabolism / Q000627:therapeutic use*; D014855:Wallerian Degeneration / Q000473:pathology
chemical_list: D018696:Neuroprotective Agents; D011951:Receptors, Complement; C082885:soluble complement inhibitor 1