Novel signalling pathways resolving the inflammatory response during peripheral nerve regeneration
type: CreativeWork
description: Introduction. The peripheral nervous system has the remarkable capacity to regenerate and restore function following damage or disease. Instrumental in this regenerative process are macrophages, Schwann cells and the production of inflammatory cytokines. The production of inflammatory cytokines from macrophages and Schwann cells needs to be tightly regulated to ensure efficient regeneration and to prevent chronic inflammation. Currently there is limited knowledge regarding which signalling pathways act to control both the inflammatory response and macrophage efflux that allows tissue homeostasis to resume within the peripheral nerves. This thesis aims to investigate the expression pattern and distinct function of VIP and PACAP and their receptors VPAC1, VPAC2 and PAC1 in the peripheral nerve post injury and how signalling through these receptors can act to promote resolution of the inflammatory response. Once macrophages have executed their function, they are required to leave the peripheral nerve to prevent chronic inflammation. There is only one macrophage efflux mechanism currently described in the peripheral nerves, where the NOGO receptors interacts with myelin to promote macrophage clearance. EphA5 has been shown to be upregulated in various RNA sequencing data sets and can induce contact dependent migratory behaviour within cells. EphA5-EphrinA signalling as a potential mechanism to induce macrophage migration and efflux out of the peripheral nerve was investigated. Methods. This project uses a combination of in vitro, ex vivo and in vivo models, including primary macrophage and Schwann cell cultures and mouse sciatic nerve cut and crush injury models to establish the function of VIP and PACAP and EphA5-EphrinA signalling at various time points throughout peripheral nerve regeneration. Results. My results show VPAC1, VPAC2, and PAC1 to be up-regulated in the mouse distal nerve following peripheral nerve injury and are highly expressed in Schwann cells and mac…
abstract: Introduction. The peripheral nervous system has the remarkable capacity to regenerate and restore function following damage or disease. Instrumental in this regenerative process are macrophages, Schwann cells and the production of inflammatory cytokines. The production of inflammatory cytokines from macrophages and Schwann cells needs to be tightly regulated to ensure efficient regeneration and to prevent chronic inflammation. Currently there is limited knowledge regarding which signalling pathways act to control both the inflammatory response and macrophage efflux that allows tissue homeostasis to resume within the peripheral nerves. This thesis aims to investigate the expression pattern and distinct function of VIP and PACAP and their receptors VPAC1, VPAC2 and PAC1 in the peripheral nerve post injury and how signalling through these receptors can act to promote resolution of the inflammatory response. Once macrophages have executed their function, they are required to leave the peripheral nerve to prevent chronic inflammation. There is only one macrophage efflux mechanism currently described in the peripheral nerves, where the NOGO receptors interacts with myelin to promote macrophage clearance. EphA5 has been shown to be upregulated in various RNA sequencing data sets and can induce contact dependent migratory behaviour within cells. EphA5-EphrinA signalling as a potential mechanism to induce macrophage migration and efflux out of the peripheral nerve was investigated. Methods. This project uses a combination of in vitro, ex vivo and in vivo models, including primary macrophage and Schwann cell cultures and mouse sciatic nerve cut and crush injury models to establish the function of VIP and PACAP and EphA5-EphrinA signalling at various time points throughout peripheral nerve regeneration. Results. My results show VPAC1, VPAC2, and PAC1 to be up-regulated in the mouse distal nerve following peripheral nerve injury and are highly expressed in Schwann cells and mac…
author: Woodley, Patricia Kate
language: eng
keywords: Peripheral nerve, Peripheral nerve injury, Regeneration, Macrophage
date published: 2022-01-01T08:00:00Z
date modified: 2026-07-24T03:50:23Z
provider: University of Plymouth
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Plymouth