Chondroitin sulphate proteoglycans: key modulators of spinal cord and brain plasticity

Abstract

Chondroitin sulphate proteoglycans (CSPGs) are a family of inhibitory extracellular matrix molecules that are highly expressed during development, where they are involved in processes of pathfinding and guidance. CSPGs are present at lower levels in the mature CNS, but are highly concentrated in perineuronal nets where they play an important role in maintaining stability and restricting plasticity. Whilst important for maintaining stable connections, this can have an adverse effect following insult to the CNS, restricting the capacity for repair, where enhanced synapse formation leading to new connections could be functionally beneficial. CSPGs are also highly expressed at CNS injury sites, where they can restrict anatomical plasticity by inhibiting sprouting and reorganisation, curbing the extent to which spared systems may compensate for the loss function of injured pathways. Modification of CSPGs, usually involving enzymatic degradation of glycosaminoglycan chains from the CSPG molecule, has received much attention as a potential strategy for promoting repair following spinal cord and brain injury. Pre-clinical studies in animal models have demonstrated a number of reparative effects of CSPG modification, which are often associated with functional recovery. Here we discuss the potential of CSPG modification to stimulate restorative plasticity after injury, reviewing evidence from studies in the brain, the spinal cord and the periphery.