Abstract
Reactive astrocytes contribute to glial scarring by rapid proliferation and up-regulation of glial fibrillary acidic protein (GFAP) expression and production of chondroitin sulfate proteoglycans (CSPGs). CSPGs play a crucial role in formation of the glial scar, which takes over the lesion site following spinal cord injury (SCI). This process corresponds to the inflammatory response of macrophages, which polarize toward a dominant pro-inflammatory M1 phenotype following SCI. The M1 phenotype is known to release various cytotoxic compounds that exacerbate the glial scar, which in turn impedes tissue regeneration. Recent studies have shown that anti-inflammatory M2 macrophages play a role in allowing neurite extensions to occur, even across inhibitory substrates, and can lessen the degree of secondary damage. Based on earlier results demonstrating that keratin biomaterials may polarize macrophages toward an anti-inflammatory M2 phenotype, we test the hypothesis that these polarized macrophages will have the potential to indirectly effect astrogliosis. Using an in vitro model of reactive astrogliosis, macrophage-conditioned media from cells that have been cultured with soluble keratin for 24 hours or 7 days appears to decrease reactivity and associates CSPG production. These results are statistically similar to the control M2 macrophage conditioned media. A comparable collagen-conditioned macrophage media does not resolve astrocyte reactivity, while control M1 macrophage conditioned media results in an increase in GFAP expression. These data suggest keratin-derived macrophages are more functionally similar to M2 macrophages and that keratin treatment may aid in limiting secondary inflammatory-mediated damage.
Highlights
One of the more pronounced late-stage outcomes following a spinal cord injury (SCI) is the formation of an astroglial scar, a reactive process that involves glial cells, mostly astrocytes, accumulating and enveloping the injury site [1]-[3]
When reactive astrocytes were cultured with macrophage media (RA-RPMI) there was no statistical difference in aggrecan, versican, or CS-56 compared to RA-astrocyte medium (AM) (Figures 1(A)-(C))
Reactive astrogliosis is heavily implicated in the development and propagation of the glial scar forming at the site of SCI
Summary
One of the more pronounced late-stage outcomes following a spinal cord injury (SCI) is the formation of an astroglial scar, a reactive process that involves glial cells, mostly astrocytes, accumulating and enveloping the injury site [1]-[3]. A dense network of glial cells and their processes physically block advancement of the growth cone, while inhibitory molecules and cytotoxic compounds held within the extracellular matrix (ECM) of the scar present chemical barriers to axon growth [6]. Chondroitin sulphate proteoglycans (CSPGs) are structural biomolecules that make up a major class of inhibitory substrates found within the glial scar but a normal component in the central nervous system (CNS). Their role in the CNS appears to be in controlling neuronal differentiation by guiding axons and restricting growth to only those proper targets, as well as preventing migration of neural crest cells, both crucial steps in neuronal development [7]-[9]. CSPGs have been shown to regulate neuronal plasticity by forming perineuronal nets around synapses [10] [11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
