A recent neural phosphoproteomics study, Selleck BAY 80-6946 which quantitatively assessed global changes in protein phosphorylation induced by CSPGs on primary CGNs, reports hits with a degree of overlap to these signalling pathways [175]. The expression pattern of specific CSPGs, and their up- or down-regulation, following brain and spinal cord injury have been defined in a number

of different injury models (see Table 1 for a summary of CSPG changes reported in the literature in experimental studies of brain and spinal cord injury in the rat). The specific sulphation motifs implicated in CSPG-mediated inhibition are less well characterized, with contradictory reports as to their relative expression and roles in guidance and repair [184–188]. These contradictory findings are partly due to analysis of heterogenous epitope substrates. However, by utilizing specific chemically synthesized homogenously sulphated CS-E oligosaccharides, it was demonstrated that the sugar epitope CS-E is potently inhibitory to growth, acting through RPTPσ via the Rho/ROCK signalling

pathway [189]. CS-E is also specifically able to localize the negative guidance cue sema3A in PNNs [49]. We may intuitively consider a range of approaches to target the inhibitory properties MK-8669 in vitro of the ECM when designing strategies to promote repair following injury to the CNS. A distinction can be drawn between preventing synthesis of particular matrix molecules after injury, and approaches designed to attenuate inhibitory properties of those molecules which are either upregulated in the scar or already existing components of the adult ECM. An approach to neural repair which directly aims to harness the biophysical and interactive properties of HA is its injection alongside methylcellulose gel to an injury site. This method alone was found to improve functional locomotor recovery following compressive spinal cord injury [190] and increased sensorimotor function when utilized as a Casein kinase 1 scaffold for cellular transplantation following spinal compression injury

[191]. Following in vitro studies showing enhanced neurite outgrowth on inhibitory CSPG-secreting cell lines by blocking NG2 [68], NG2 function blocking antibodies have been applied in vivo. Following dorsal column transection of the spinal cord, regenerative growth of sensory axons was moderately enhanced by NG2 antibody treatment, an effect augmented by a peripheral nerve conditioning lesion [192]. Acute application of NG2 to the spinal cord has also been shown to block axonal conduction dose-dependently [193], a response which is ameliorated by delivery of an NG2 antibody [194]. Another repair promoting strategy has involved enhancing the expression of CSPG-depleting ECM components such as decorin.