Complement inhibition accelerates regeneration in a model of peripheral nerve injury

Valeria Ramaglia, Martijn Rudolf Tannemaat, Maryla de Kok, Ruud Wolterman, Miriam Ann Vigar, Rosalind Helen Mary King, Bryan Paul Morgan, Frank Baas

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23 Citations (Scopus)

Abstract

Complement (C) activation is a crucial event in peripheral nerve degeneration but its effect on the subsequent regeneration is unknown. Here we show that genetic deficiency of the sixth C component, C6, accelerates axonal regeneration and recovery in a rat model of sciatic nerve injury. Foot-flick test and Sciatic Function Index monitored up to 5 weeks post-injury showed a significant improvement of sensory and motor function in the C6 deficient animals compared to wildtypes. Retrograde tracing experiments showed a significantly higher number of regenerated neurons at 1 week post-injury in C6 deficient rats than wildtypes. Pathology showed improved nerve regeneration in tibials of C6 deficient animals compared to wildtypes. Reconstitution with purified human C6 protein re-established the wildtype phenotype whereas pharmacological inhibition of C activation with soluble C receptor 1 (sCR1) facilitated recovery and improved pathology similarly to C6 deficient animals. We suggest that a destructive C-mediated event during nerve degeneration hampers the subsequent regenerative process. These findings provide a rationale for the testing of anti-complement agents in human nerve injury. (C) 2009 Elsevier Ltd. All rights reserved
Original languageEnglish
Pages (from-to)302-309
JournalMolecular immunology
Volume47
Issue number2-3
DOIs
Publication statusPublished - 2009

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