CS-4,6 is differentially upregulated in glial scar and is a potent inhibitor of neurite extension

Gilbert, Ryan J.; McKeon, Robert J.; Darr, Adnan; Calabro, Anthony; Hascall, Vincent C.; Bellamkonda, Ravi V.

doi:10.1016/j.mcn.2005.04.006

Cited by 157 publications

(157 citation statements)

References 50 publications

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“…Several lines of evidence support the importance of differentially sulfated CS-GAGs in controlling axon regeneration following CNS injury, with 4S being inhibitory while 6S is either inhibitory or permissive (Gilbert et al, 2005;Lin et al, 2011;Properzi et al, 2005;Wang et al, 2008). Using antibodies specific for sulfation patterns on GAG chains, we detected an increased level of 4S, but not 6S, in a tight band around the injury core, overlapping with the neurocan staining.…”

Section: Discussionsupporting

confidence: 51%

“…It has been proposed that the sulfation pattern on the GAGs confers specific biological activity on axonal growth, either inhibiting (Gilbert et al, 2005;Properzi et al, 2005;Wang et al, 2008) or promoting (Gama et al, 2006;Lin et al, 2011) growth. The majority of CS-GAG sulfation in the mammalian central nervous system is found as disaccharides with a sulfate group on the 4 or 6 position of GalNAc (Ishii and Maeda, 2008;Kitagawa et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice

Katagiri

Susarla

et al. 2012

J of Comparative Neurology

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Chondroitin sulfate proteoglycans (CSPGs) play a pivotal role in many neuronal growth mechanisms including axon guidance and the modulation of repair processes following injury to the spinal cord or brain. Many actions of CSPGs in the central nervous system (CNS) are governed by the specific sulfation pattern on the glycosaminoglycan (GAG) chains attached to CSPG core proteins. To elucidate the role of CSPGs and sulfated GAG chains following traumatic brain injury (TBI), controlled cortical impact injury of mild to moderate severity was performed over the left sensory motor cortex in mice. Using immunoblotting and immunostaining, we found that TBI resulted in an increase in the CSPGs neurocan and NG2 expression in a tight band surrounding the injury core, which overlapped with the presence of 4-sulfated CS GAGs but not with 6-sulfated GAGs. This increase was observed as early as 7 days post injury (dpi), and persisted up to 28 dpi. Labeling with markers against microglia/macrophages, NG2 + cells, fibroblasts and astrocytes showed that these cells were all localized in the area, suggesting multiple origins of chondroitin-4-sultate increase. TBI also caused a decrease in the expression of aggrecan and phosphacan in the pericontusional cortex with a concomitant reduction in the number of perineuronal nets. In summary, we describe a dual response in CSPGs where they may be actively involved in complex repair processes following TBI. INDEXING TERMSChondroitin sulfate proteoglycan; traumatic brain injury; extracellular matrix; perineuronal nets

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Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 99%

Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice

Katagiri

Susarla

et al. 2012

J of Comparative Neurology

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“…An optimized decellularization process for nucleus pulposus needs to balance the removal of cells with the maintenance of sGAGs. The sGAGs are essential in maintaining the osmotic pressure of the nucleus pulposus [8], and they have the potential to play a role in driving cell phenotype [45][46][47]50,58] and preventing innervation [59][60][61][62]. The gentle decellularization protocol used in our laboratory for nerve [39,43,63] and lung tissue [38] was adapted for use in the nucleus pulposus by shortening the duration of wash cycles substantially.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, our confocal results indicate preservation of CSPGs after decellularization. CSPGs are known to be potent neurite inhibitors [11,12,60,64]. By maintaining CSPG presence in the matrix, this has the potential to prevent nerve growth into the nucleus pulposus.…”

Section: Discussionmentioning

confidence: 99%

Creation of an injectable in situ gelling native extracellular matrix for nucleus pulposus tissue engineering

et al. 2017

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Background Context: Disc degeneration is the leading cause of low back pain and is often characterized by a loss of disc height, resulting from cleavage of chondroitin sulfate proteoglycans (CSPGs) present in the nucleus pulposus. Intact CSPGs are critical to water retention and maintenance of the nucleus osmotic pressure. Decellularization of healthy nucleus pulposus tissue has the potential to serve as an ideal matrix for tissue engineering of the disc because of the presence of native disc proteins and CSPGs. Injectable in situ gelling matrices are the most viable therapeutic option to prevent damage to the anulus fibrosus and future disc degeneration.

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“…After lesions, CSPGs are upregulated several-fold, peaking at between 10 to 14 days post-lesion [2] . Together with activated glial cells, the CSPGs form a dense layer of glial scar inhibitory to axon growth, and much of this inhibition is due to the activity of the glycosaminoglycan (GAG) chains [3] . in addition, CSPGs are major components of the perineuronal nets (PNNs), which are dense ECM structures that form around many neuronal cell bodies and dendrites late in development [4,5] .…”

Section: Introductionmentioning

confidence: 99%

Combination treatment with chondroitinase ABC in spinal cord injury—breaking the barrier

Zhao

Fawcett

2013

Neurosci. Bull.

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After spinal cord injury (SCi), re-establishing functional circuitry in the damaged central nervous system (CNS) faces multiple challenges including lost tissue volume, insufficient intrinsic growth capacity of adult neurons, and the inhibitory environment in the damaged CNS. Several treatment strategies have been developed over the past three decades, but successful restoration of sensory and motor functions will probably require a combination of approaches to address different aspects of the problem. Degradation of the chondroitin sulfate proteoglycans with the chondroitinase ABC (ChABC) enzyme removes a regeneration barrier from the glial scar and increases plasticity in the CNS by removing perineuronal nets. its mechanism of action does not clash or overlap with most of the other treatment strategies, making ChABC an attractive candidate as a combinational partner with other methods. in this article, we review studies in rat SCi models using ChABC combined with other treatments including cell implantation, growth factors, myelin-inhibitory molecule blockers, and ion channel expression. We discuss possible ways to optimize treatment protocols for future combinational studies. To date, combinational therapies with ChABC have shown synergistic effects with several other strategies in enhancing functional recovery after SCi. These combinatorial approaches can now be developed for clinical application.

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CS-4,6 is differentially upregulated in glial scar and is a potent inhibitor of neurite extension

Cited by 157 publications

References 50 publications

Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice

Alterations in sulfated chondroitin glycosaminoglycans following controlled cortical impact injury in mice

Creation of an injectable in situ gelling native extracellular matrix for nucleus pulposus tissue engineering

Combination treatment with chondroitinase ABC in spinal cord injury—breaking the barrier

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