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 Lapatinib research buy 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. The extracellular matrix (ECM) of the central nervous system (CNS) forms a large component of brain and spinal cord tissue, consisting of a dense substrata which occupies the space between neurones and glia, estimated to comprise 10–20% of the total brain volume . It contains a diverse array of molecules, largely secreted by Gefitinib order cells of the CNS, and has functions beyond passive provision of a supportive framework: it actively influences cell migration, axonal guidance and synaptogenesis during development and in adulthood plays an important role in maintaining synaptic stability and restricting aberrant remodelling. However, following injury or disease to the CNS, changes in the expression and composition of ECM components can prove detrimental to neural repair. Therefore, strategies to manipulate the ECM can be applied following injury or disease of the brain and Urease spinal cord. These will be discussed below. The ECM in the CNS is specialized. With the exception of the meninges, vasculature and blood-brain barrier (BBB), it lacks the proportion of fibrillar collagens and fibronectin that are typically found in the
ECM of systemic tissues (such as cartilage). Instead, the CNS ECM is rich in glycoproteins and proteoglycans. Figure 1A shows the typical composition of the ECM and how the various ECM components interact. The core component hyaluronan (HA; also known as hyaluronic acid or hyaluronate) forms a backbone for the attachment of other glycoproteins and proteoglycans. This principally includes tenascins and sulphated proteoglycans, stabilized by link proteins. These components may be arranged diffusely in the interstitial space or into more condensed structures which comprise small ‘axonal coats’ encapsulating presynaptic terminal fibres and synaptic boutons, clustered matrix assemblies around nodes of Ranvier and perineuronal nets (PNNs) surrounding the cell soma, proximal dendrites and axon initial segments of some neurones [2,3].