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

Abstract

Brain and spinal cord injury can result in permanent cognitive, motor, sensory and autonomic deficits. The central nervous system (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 neurones, its role is not only structural; the ECM is homeostatic, actively regulatory and of great signalling importance, both directly via receptor or coreceptor-mediated action and via spatially and temporally relevant localization 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.

Keywords: extracellular matrix; plasticity; spinal cord injury.