An in vitro model of the inhibition of axon growth in the lesion scar formed after central nervous system injury

Kimura‐Kuroda, Junko; Teng, Xichuan; Komuta, Yukari; Yoshioka, Nozomu; Sango, Kazunori; Kawamura, Koki; Raisman, Geoffrey; Kawano, Hitoshi

doi:10.1016/j.mcn.2009.10.008

Cited by 52 publications

(64 citation statements)

References 61 publications

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“…We have previously demonstrated that neurite outgrowth of cerebellar neurons is severely inhibited on cell clusters induced by TGF-b1, but the mechanism was not yet known. 17 Addition of ChABC or ChAC to TGF-b1-induced cell clusters reduced not only the CS immunoreactivity but also the inhibitory property of the cluster (Fig. 7).…”

Section: Role Of Gags On Axonal Regeneration In the Cnsmentioning

confidence: 91%

“…When neonatal cerebellar neurons were grown on the coculture in the absence of TGF-b1, neurons expressed an intense preference for astrocytes over fibroblasts as reported previously. 17 Treatment of this co-culture with three kinds of chondroitinases did not affect the neurite outgrowth. Further, neurite outgrowth on PLL-coated dishes was not changed by treatment with any of three kinds of chondroitinases.…”

mentioning

confidence: 86%

“…5Ai), which expressed a high amount of CS and intensely repelled neuritis. 17 In the present study, how GAGs are involved in the scar-forming activity of TGF-b1was examined. Incubation of the coculture with 0.1 U/mL of ChB or ChABC significantly suppressed the cluster formation (Fig.…”

mentioning

confidence: 93%

“…15,16 Further, we have recently established an in vitro model of lesion scar formation in which addition of transforming growth factor-b1 (TGF-b1) to the co-culture of meningeal fibroblasts and cerebral astrocytes induces the formation of fibrotic scar-like cell clusters. 17 Using this model, effects of chondroitinases on the cell cluster formation and neurite outgrowth were also examined.…”

mentioning

confidence: 99%

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Roles of Chondroitin Sulfate and Dermatan Sulfate in the Formation of a Lesion Scar and Axonal Regeneration after Traumatic Injury of the Mouse Brain

Liu

Komuta

Kimura‐Kuroda

et al. 2013

Journal of Neurotrauma

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Dermatan sulfate (DS) is synthesized from chondroitin sulfate (CS) by epimerization of glucuronic acid of CS to yield iduronic acid. In the present study, the role of CS and DS was examined in mice that received transection of nigrostriatal dopaminergic pathway followed by injection of glycosaminoglycan degrading enzymes into the lesion site. Two weeks after injury, fibrotic and glial scars were formed around the lesion, and transected axons did not regenerate beyond the fibrotic scar. Injection of chondroitinase ABC (ChABC), which degrades both CS and DS, completely suppressed the fibrotic scar formation, reduced the glial scar, and promoted the regeneration of dopaminergic axons. Injection of the DSdegrading enzyme chondroitinase B (ChB) also yielded similar results. By contrast, injection of chondroitinase AC (ChAC), a CS-degrading enzyme, did not suppress the fibrotic and glial scar formation, but reduced CS immunoreactivity and promoted the axonal regeneration. Addition of transforming growth factor-b1 (TGF-b1) to a co-culture of meningeal fibroblasts and cerebral astrocytes induces a fibrotic scar-like cell cluster. The effect of TGF-b1 on cluster formation was suppressed by treatment with ChABC or ChB, but not by ChAC. TGF-b1-induced cell cluster repelled neurites of neonatal cerebellar neurons, but addition of ChABC or ChAC suppressed the inhibitory property of clusters on neurite outgrowth. The present study is the first to demonstrate that DS and CS play different functions after brain injury: DS is involved in the lesion scar formation, and CS inhibits axonal regeneration.

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Section: Role Of Gags On Axonal Regeneration In the Cnsmentioning

confidence: 91%

mentioning

confidence: 86%

mentioning

confidence: 93%

mentioning

confidence: 99%

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Roles of Chondroitin Sulfate and Dermatan Sulfate in the Formation of a Lesion Scar and Axonal Regeneration after Traumatic Injury of the Mouse Brain

Liu

Komuta

Kimura‐Kuroda

et al. 2013

Journal of Neurotrauma

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“…In vitro fibrotic scars constructed from primary cultures of neurons growing on primary co-cultures of astrocytes and fibroblasts treated with transforming growth factor β1 (TGFβ1; Kimura-Kuroda et al 2010) represent a model that shows very similar molecular and biochemical features to actual CNS lesions. Neurons growing in this model avoid the scar, shorten their axons and lose appropriate synaptic plasticity.…”

Section: Glia Limitansmentioning

confidence: 99%

Calcium transporters and their role in the development of neuronal disease and neuronal damage

Jašková

Pavlovicova²,

Jurkovičová³

2012

gpb

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Abstract. Neurodegeneration comprises assembly of pathophysiological events that gives rise to a progressive loss of neuronal structure and function including cellular damage, diseases development or cellular death. Neurons respond by adjusting signaling pathways, from gene expression to morphological changes. In most of these processes, Ca 2+ signaling plays a pivotal role. By increasing the Ca 2+ concentration, the cell responds to neuronal, neurotrophic and other growth factor stimuli, however, the molecular mechanism of Ca 2+ -dependent neurite outgrowth and development yet requires further elucidation.Here we focus on the role of Ca 2+ and selected Ca 2+ transporters involved in processes of CNS neurodegeneration -inositol 1,4,5-trisphosphate (IP 3 Rs) and ryanodine receptors (RyRs), considering the fact that these receptors may be important "sensors" of disturbed intracellular calcium homeostasis. We propose that in vitro cellular models could serve as suitable experimental systems for the determination of the role that these receptors play in neuropathological conditions.Recognition of the principles, key players and regulatory processes may elucidate the role of Ca 2+ in the regulation of neuronal proliferation, development and differentiation, growth and axon navigation in neurodegenerative and regenerative processes. This may provide a new insight and also discovery of novel therapeutic-targeting possibilities for severe neurological disorders and pathophysiological changes.

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Prevented Cell Clusters’ Migration Via Microdot Biomaterials for Inhibiting Scar Adhesion

Zhuang,

Lin,

Xiang

et al. 2024

Advanced Materials

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Cluster‐like collective cell migration of fibroblasts is one of the main factors of adhesion in injured tissues. In this research, a microdot biomaterial system was constructed using α‐helical polypeptide nanoparticles and anti‐inflammatory micelles, which were prepared by ring‐opening polymerization of α‐amino acids‐N‐carboxylic anhydrides (NCAs) and lactide, respectively. The microdot biomaterial system slowly released functionalized polypeptides targeting mitochondria and promoting the influx of extracellular calcium ions under the inflammatory environment, thus inhibiting the expression of N‐cadherin mediating cell‐cell interaction, and promoting apoptosis of cluster fibroblasts, synergistically inhibiting the migration of fibroblast clusters at the site of tendon injury. Meanwhile, the anti‐inflammatory micelles in the microdot biomaterial system were celecoxib (Cex) solubilized by PEG/polyester, which could improve the inflammatory microenvironment at the injury site for a long time. In vitro, the microdot biomaterial system could effectively inhibit the migration of the cluster fibroblasts by inhibiting the expression of N‐cadherin between cell‐cell and promoting apoptosis. In vivo, the microdot biomaterial system could promote apoptosis while achieving long‐acting anti‐inflammation effects, and reduce the expression of vimentin and α‐smooth muscle actin in fibroblasts. Thus, this microdot biomaterial system provided new ideas for the prevention and treatment of tendon adhesion by inhibiting the cluster migration of fibroblasts.This article is protected by copyright. All rights reserved

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An in vitro model of the inhibition of axon growth in the lesion scar formed after central nervous system injury

Cited by 52 publications

References 61 publications

Roles of Chondroitin Sulfate and Dermatan Sulfate in the Formation of a Lesion Scar and Axonal Regeneration after Traumatic Injury of the Mouse Brain

Roles of Chondroitin Sulfate and Dermatan Sulfate in the Formation of a Lesion Scar and Axonal Regeneration after Traumatic Injury of the Mouse Brain

Calcium transporters and their role in the development of neuronal disease and neuronal damage

Prevented Cell Clusters’ Migration Via Microdot Biomaterials for Inhibiting Scar Adhesion

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An in vitro model of the inhibition of axon growth in the lesion scar formed after central nervous system injury

Cited by 52 publications

References 61 publications

Roles of Chondroitin Sulfate and Dermatan Sulfate in the Formation of a Lesion Scar and Axonal Regeneration after Traumatic Injury of the Mouse Brain

Roles of Chondroitin Sulfate and Dermatan Sulfate in the Formation of a Lesion Scar and Axonal Regeneration after Traumatic Injury of the Mouse Brain

Calcium transporters and their role in the development of neuronal disease and neuronal damage

Prevented Cell Clusters’ Migration Via Microdot Biomaterials for Inhibiting Scar Adhesion

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Product

Resources

About

Calcium transporters and their role in the development of neuronal disease and neuronal damage