Furthermore, developmental increase in the ratio of four sulphated to six sulphated CSPGs has been shown to terminate the critical period for ocular dominance plasticity, associated with expression of the homeoprotein Otx2 and associated transcriptional activation of mature firing dynamics [124,125]. Thus, the CNS ECM plays an important role during development, with the expression selleck chemicals and localization of ECM components forming a central part of many fundamental developmental processes, including axon guidance and regulation of synaptic plasticity. However, the gross expression and mass accumulation of ECM molecules around areas of CNS injuries, or in regions of degeneration,

act to restrict growth, axon elongation, sprouting and plasticity. These processes will be reviewed in the following section. After CNS injury the composition of the ECM is altered dramatically. This is influenced by which cells are subsequently localized to the lesion site, in turn likely to be dependent on the nature of the injury.

For example, following blunt trauma that results in disruption of the BBB but where the dura mater remains intact (such is the case with contusive-type spinal cord injuries and blunt traumatic brain injuries), glia are generally considered to be the main source of scar matrix deposition, whereas penetrating spinal laceration, transection or cortical stab injuries additionally confer more Smoothened Agonist supplier significant fibroblast invasion via disrupted meninges [126]. Figure 2 shows the typical cells recruited and the expression of ECM components following a penetrating injury vs. blunt trauma

in the CNS (focusing on CSPG expression after spinal cord injury). Following CNS injury, primary axonal and vascular damage initiates a cascade of secondary pathology. BBB Methane monooxygenase permeability is increased and a neuroinflammatory response is initiated whereby the upregulation of local pro-inflammatory cytokines and chemokines occurs (reviewed in [127]). This predominantly activates astrocytes, as well as microglia and oligodendrocyte precursor cells (OPCs) to form the glial component of the injury response and the development of a glial scar. Reactive astrocytes are the main cellular constituents of the glial scar. Astrocytes may be characterized as reactive by increased expression of glial fibrillary acidic protein (GFAP). They proliferate and exhibit changes in gene expression and morphology; classically thought to undergo hypertrophy and extend overlapping processes to result in persistent scar formation (see [128] for recent review on structural changes of astrocytes in reactive gliosis). This is also associated with increased expression of TnC [129,130] and particularly sulphated proteoglycans [131].