Biomaterial Approaches to Enhancing Neurorestoration after Spinal Cord Injury: Strategies for Overcoming Inherent Biological Obstacles

Figure 2

Upregulation and expression of CSPGs. Almost immediately following an SCI, astrocytes located within the area of trauma begin to undergo hypertrophy, synthesizing and secreting CSPGs, including neurocan, phosphacan, and brevican. Additionally, the infiltration of vascular macrophages, activated microglial cells, and OPCs results in the increase in the proteoglycans NG2 and versican. The temporal expression of these proteoglycans is important to factor into any treatment, as they have differential effects on the regenerative process. Neurocan and versican are upregulated quickly following injury, with maximal expression observed 2 weeks after injury. Their expression begins to wane at longer times, approaching base levels by 8 weeks after injury. Brevican is also upregulated after injury, reaching maximal expression 2 weeks after injury. However unlike neurocan and versican, brevican expression remains elevated over time. Phosphacan is initially downregulated following SCI, with significantly reduced levels 1 week after injury. The expression begins to increase at longer times after injury and peaks around 8 weeks after injury. NG2 expression can be generally correlated to the infiltration of vascular macrophages, activated microglia, and OPCs, with maximal expression being found 1 week after injury. This differential expression pattern of CSPGs plays a large role in governing the regenerative response as many CSPGs are inhibitory to both process of atonal regeneration and remyelination (adapted from [8]).