Repair of damage to the nervous system requires axon regeneration,plasticity and cell replacement.The extracellular matrix plays a central role in restricting these processes,mainly through the action of chondroitin sulphate proteoglycans (CSPGs).An important agent in removing this restriction has been the enzyme chondroitinase,which removes glycosaminoglycan (GAG) chains from CSPGs.CSPGs are upregulated in glial scar tissue around injuries to restrict axon regeneration,which can be enhanced with chondroitinase.However the positive effect of chondroitinase on functional recovery is mostly through reactivation of plasticity.Chondroitinase treatment enhances recovery from many forms of CNS damage,including spinal cord injury,where the reactivation of plasticity enables successful rehabilitation.Chondroitinase also has profound effects on memory,prolonging object memory in normal animals and restoring memory in an Alzheimers model.CPSGs control plasticity mainly through their participation in perineuronal nets (PNNs),cartilage-like structures surrounding neurons,which appear as critical periods for plasticity close.PNNs contain inhibitory CSPGs,hyaluronan,link protein and tenascin R,partly produced by the neurones themselves and partly by surrounding glial cells.All neurones with PNNs express both a hyaluronan synthase enzyme and a link protein,and these are the key components that trigger the formation of the structures.Link protein knockout animals lack normal PNNs on their dendrites,and these animals retain plasticity into adulthood,and show prolongation of memory identically to animals treated with chondrotinase.The action of the CSPGs is due to their sulphated GAGs.In the CNS these bind to and localise Semaphorin3A and OTX2 to PNNs.OTX2 is involved in the maturation of inhibitory interneurons,while Semaphorin3A is an effector of the PNNs involved in control of plasticity.