Manipulating the extracellular matrix and its role in brain and spinal cord plasticity and repair

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http://onlinelibrary.wiley.com/doi/10.1111/nan.12114/abstract

1. Emily R. Burnside,
2. Elizabeth J. Bradbury^*

DOI: 10.1111/nan.12114

This article is protected by copyright. All rights reserved.

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Neuropathology and Applied Neurobiology

Accepted Article (Accepted, unedited articles published online and citable. The final edited and typeset version of record will appear in future.)

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1. This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/nan.12114

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Abstract

Brain and spinal cord injury can result in permanent cognitive, motor, sensory and autonomic deficits. The CNS has a poor intrinsic capacity for regeneration, although some functional recovery does occur. This is mainly in the form of sprouting, dendritic remodelling and changes in neuronal coding, firing and synaptic properties; elements collectively known as plasticity. An important approach to repair the injured CNS is therefore to harness, promote and refine plasticity. In the adult, this is partly limited by the extracellular matrix (ECM). While the ECM typically provides a supportive framework to CNS neurons, its role is not only structural; the ECM is homeostatic, actively regulatory and of great signalling importance, both directly via receptor or co-receptor-mediated action and via spatially and temporally relevant localisation of other signalling molecules. In an injury or disease state, the ECM represents a key environment to support a healing and/or regenerative response. However, there are aspects of its composition which prove suboptimal for recovery: some molecules present in the ECM restrict plasticity and limit repair. An important therapeutic concept is therefore to render the ECM environment more permissive by manipulating key components, such as inhibitory chondroitin sulphate proteoglycans. In this review we discuss the major components of the ECM and the role they play during development and following brain or spinal cord injury and we consider a number of experimental strategies which involve manipulations of the ECM, with the aim of promoting functional recovery to the injured brain and spinal cord.

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