# Roles of the Complement System in Peripheral Nerve Injury and Repair

## TL;DR

This paper reviews how the complement system influences nerve injury and repair, focusing on acute and chronic injury states.

## Contribution

The paper systematically reviews the role of the complement system in peripheral nerve injury and identifies knowledge gaps.

## Key findings

- Chronic injury is marked by extracellular matrix changes and loss of neurotrophic factors.
- Complement pathways may significantly influence nerve repair and immune responses.
- Systemic effects of nerve injury include impacts on muscles and bones.

## Abstract

When nerves are severed, such as during traumatic injury, an acute injury state is induced, characterized by biological and physical changes in the proximal and distal stumps. Beyond the initial injury phase, over a time frame of weeks to months, nerves that remain unrepaired progressively enter a chronic injury state, characterized by a change in the extracellular matrix structure of the distal stump, the down-regulation of neurotrophic factors and the loss of macrophages’ and Schwann cells’ ability to clear out degraded axons and myelin. There are also potential systemic impacts away from the site of injury, including in end organs such as muscle and bone. The literature suggests that several of these processes may be strongly influenced by innate and adaptive immune system responses, including a major role for complement pathways. This review details evidence in favor of such a possibility, as well as knowledge gaps and areas for future investigation.