NG2 and phosphacan are present in the astroglial scar after human traumatic spinal cord injury

Abstract

Background: A major class of axon growth-repulsive molecules associated with CNS scar tissue is the family of chondroitin sulphate proteoglycans (CSPGs). Experimental spinal cord injury (SCI) has demonstrated rapid reexpression of CSPGs at and around the lesion site. The pharmacological digestion of CSPGs in such lesion models results in substantially enhanced axonal regeneration and a significant functional recovery. The potential therapeutic relevance of interfering with CSPG expression or function following experimental injuries seems clear, however, the spatio-temporal pattern of expression of individual members of the CSPG family following human spinal cord injury is only poorly defined. In the present correlative investigation, the expression pattern of CSPG family members NG2, neurocan, versican and phosphacan was studied in the human spinal cord.

Chondroitin Sulfate Proteoglycans Negatively Modulate Spinal Cord Neural Precursor Cells by Signaling Through LAR and RPTPσ and Modulation of the Rho/ROCK Pathway

“…Replacement of oligodendrocytes is an essential approach for remyelination and functional repair following SCI [3,4]. Here, we used a direct in vitro system to model the ECM of SCI where laminin and CSPGs are highly elevated [27,28]. When exposed to a matrix containing CSPGs, adult NPCs showed a significant decrease in their ability to integrate, grow, proliferate, and survive.…”

“…Importantly, aggrecan directly inhibits laminin-mediated axon growth by impairing integrin signaling through decreasing phosphorylated FAK and Src levels [58,59]. Notably, aggrecan was included in our CSPGs mixture and our substrate also contained laminin to more closely represent the ECM composition of SCI [27]. Thereby, it is plausible that blockade of integrin/laminin signaling in NPCs partly underlined the inhibitory effects of CSPGs independent of LAR and/or RPTPr.…”

“…1A-1D). Laminin and CSPGs are highly upregulated in the ECM of the injured spinal cord and therefore laminin1CSPGs condition would more closely represent the milieu of SCI [27,28]. We used CSPGs substrate containing a mixture of neurocan, phosphocan, versican, and aggrecan that are present in the ECM of SCI [28].…”