Complement inhibition accelerates regeneration in a model of peripheral nerve injury

Ramaglia, Valeria, Tannemaat, Martijn Rudolf, de Kok, Maryla, Wolterman, Ruud, Vigar, Miriam Ann, King, Rosalind Helen Mary, Morgan, Bryan Paul ORCID: https://orcid.org/0000-0003-4075-7676 and Baas, Frank 2009. Complement inhibition accelerates regeneration in a model of peripheral nerve injury. Molecular Immunology 47 (2-3) , pp. 302-309. 10.1016/j.molimm.2009.09.019

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Uncontrolled Keywords:	Crush injury; Complement; Complement inhibitors; Regeneration; Recovery
Publisher:	Elsevier
ISSN:	0161-5890
Last Modified:	19 Oct 2022 10:48
URI:	https://orca.cardiff.ac.uk/id/eprint/25597

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