Studies of plasticity after neuronal injury
type: CreativeWork
description: Neurons of the adult mammalian central nervous system (CNS) and peripheral nervous system (PNS) differ in their response to injury. PNS neurons have a robust growth response and are capable of regenerating their axons and reinnervating peripheral targets following nerve injury. However, despite this robust regenerative response, specificity of target reinnervation is often poor, leading to a suboptimal functional outcome. In contrast, injured CNS neurons have a poor growth response and completely fail to regenerate, but uninjured axons that survive the injury undergo some degree of spontaneous reorganisation that is accompanied by limited functional improvement. In theory, appropriate reorganisation of central connections could compensate for topographical errors in the periphery and enhancing the innate capacity for reorganisation after CNS injury could compensate for lost function. Thus, recovery from both types of injury may benefit from strategies to enhance CNS plasticity. This Thesis makes use of an experimental strategy to promote plastic changes, that is, the enzyme chondroitinase ABC (ChABC) which degrades chondroitin sulphate proteoglycans - a major class of inhibitory extracellular matrix molecules. Viral vector technology was used to optimise the delivery of ChABC by gene transfer to host spinal cord cells. A lentiviral vector expressing the ChABC gene (LV-ChABC) was delivered to the adult rat spinal cord to achieve long-term delivery of active ChABC in vivo. After peripheral nerve injury, where two forelimb nerves were cut and repaired with different levels of inaccuracy, electrophysiological studies demonstrated that LV-ChABC injection led to significant plasticity of central connections, such as reorganisation of high and low threshold polysynaptic reflexes. ChABC did not lead to any changes in reflex activity in uninjured animals. These results indicate that ChABC facilitates the amplification of compensatory changes in the spinal cord following inju…
abstract: Neurons of the adult mammalian central nervous system (CNS) and peripheral nervous system (PNS) differ in their response to injury. PNS neurons have a robust growth response and are capable of regenerating their axons and reinnervating peripheral targets following nerve injury. However, despite this robust regenerative response, specificity of target reinnervation is often poor, leading to a suboptimal functional outcome. In contrast, injured CNS neurons have a poor growth response and completely fail to regenerate, but uninjured axons that survive the injury undergo some degree of spontaneous reorganisation that is accompanied by limited functional improvement. In theory, appropriate reorganisation of central connections could compensate for topographical errors in the periphery and enhancing the innate capacity for reorganisation after CNS injury could compensate for lost function. Thus, recovery from both types of injury may benefit from strategies to enhance CNS plasticity. This Thesis makes use of an experimental strategy to promote plastic changes, that is, the enzyme chondroitinase ABC (ChABC) which degrades chondroitin sulphate proteoglycans - a major class of inhibitory extracellular matrix molecules. Viral vector technology was used to optimise the delivery of ChABC by gene transfer to host spinal cord cells. A lentiviral vector expressing the ChABC gene (LV-ChABC) was delivered to the adult rat spinal cord to achieve long-term delivery of active ChABC in vivo. After peripheral nerve injury, where two forelimb nerves were cut and repaired with different levels of inaccuracy, electrophysiological studies demonstrated that LV-ChABC injection led to significant plasticity of central connections, such as reorganisation of high and low threshold polysynaptic reflexes. ChABC did not lead to any changes in reflex activity in uninjured animals. These results indicate that ChABC facilitates the amplification of compensatory changes in the spinal cord following inju…
author: Bosch, Karen
language: eng
date published: 2013-4
date modified: 2026-07-24T02:44:34Z
provider: King's College London
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: King's College London