The microenvironment following oxygen glucose deprivation/re-oxygenation-induced BSCB damage in vitro

Cai, Xueting; Zhao, Jingjing; Lü, Yi; Zhang, Jianping; Ren, Bing-Yan; Cao, Tingting; Xi, Guangjun; Li, Zaiwang

doi:10.1016/j.brainresbull.2018.08.005

Cited by 7 publications

(16 citation statements)

References 34 publications

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“…However, STS treatment reverses these effects and indicates that STS protects SCMEC functions. Meanwhile, many studies reported that inflammation was the second major component impacting SCMEC functions and BSCB integrity [ 60 , 61 ]. Inflammatory mediators including IL-6, TNF- α , and IL-1 β can recruit inflammatory cells to invade the central nervous system through a damaged BSCB.…”

Section: Discussionmentioning

confidence: 99%

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Sodium Tanshinone IIA Silate Exerts Microcirculation Protective Effects against Spinal Cord Injury In Vitro and In Vivo

Luo

Hou

et al. 2020

Oxidative Medicine and Cellular Longevity

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Spinal cord microcirculation involves functioning endothelial cells at the blood spinal cord barrier (BSCB) and maintains normal functioning of spinal cord neurons, axons, and glial cells. Protection of both the function and integrity of endothelial cells as well as the prevention of BSCB disruption may be a strong strategy for the treatment of spinal cord injury (SCI) cases. Sodium Tanshinone IIA silate (STS) is used for the treatment of coronary heart disease and improves microcirculation. Whether STS exhibits protective effects for SCI microcirculation is not yet clear. The purpose of this study is to investigate the protective effects of STS on oxygen-glucose deprivation- (OGD-) induced injury of spinal cord endothelial cells (SCMECs) in vitro and to explore effects on BSCB and neurovascular protection in vivo. SCMECs were treated with various concentrations of STS (1 μM, 3 μM, and 10 μM) for 24 h with or without OGD-induction. Cell viability, tube formation, migration, and expression of Notch signaling pathway components were evaluated. Histopathological evaluation (H&E), Nissl staining, BSCB permeability, and the expression levels of von Willebrand Factor (vWF), CD31, NeuN, and Notch signaling pathway components were analyzed. STS was found to improve SCMEC functions and reduce inflammatory mediators after OGD. STS also relieved histopathological damage, increased zonula occludens-1 (ZO-1), inhibited BSCB permeability, rescued microvessels, protected motor neuromas, and improved functional recovery in a SCI model. Moreover, we uncovered that the Notch signaling pathway plays an important role during these processes. These results indicated that STS protects microcirculation in SCI, which may be used as a therapeutic strategy for SCI in the future.

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Section: Discussionmentioning

confidence: 99%

“…Tight junction proteins are located around the interendothelial space, sealing the BSCB [ 69 ]. Disruption of tight junction proteins may lead to BSCB permeability during SCI [ 60 ]. ZO-1 is a cytoplasmic tight junction protein that plays an important role in tight junction protein maintenance and formation [ 70 ].…”

Section: Discussionmentioning

confidence: 99%

Sodium Tanshinone IIA Silate Exerts Microcirculation Protective Effects against Spinal Cord Injury In Vitro and In Vivo

Luo

Hou

et al. 2020

Oxidative Medicine and Cellular Longevity

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“…Microvascular endothelial cells (MEC) injury in traumatic mechanical violence causes damage of the BSCB [4], which leads to a mass of peripheral in ammatory cells and pro-in ammatory cytokines that invade the spinal cord nervous tissue [5]. Dual effects of traumatic mechanical violence and in ammation trigger activation of microglia and astrocytes and incur reactive gliosis [6], which escalates in ammatory reaction, eventually causing neighboring neuron loss and demyelination [6][7][8]. Above all, in ammation following SCI can also cause BSCB damage of neighboring intact spinal cord tissue, which induces a new round of peripheral in ammatory cells and factors that invade the spinal cord tissue and activate a cascade of secondary damage processes (the damage positive feedback) [6,8].…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…In short, the pathogenesis of secondary injury after SCI is closely related to the damage positive feedback, which is formed by damage of BSCB and the ensuing in ammatory injury evoking neural tissue damage [8,9]. The destruction of BSCB plays a key role in the pathogenesis of secondary injury after SCI [8]. Therefore, protecting the structural and functional integrity of BSCB after SCI is crucial to control secondary damage and reconstruct the spinal cord neural tissue microenvironment homeostasis after SCI [8,10,11].…”

Section: Introductionmentioning

confidence: 99%

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Blocking the EGFR/p38/NF-κB Signal Pathway Alleviates Disruption of BSCB and Subsequent Inflammation After Spinal Cord Injury

Zhao

et al. 2021

Preprint

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Background:Epidermal growth factor receptor (EGFR) activation may play an important role in blood spinal cord barrier (BSCB) disruption and secondary injury after SCI as it is significantly upregulated in the astrocytes (AS) and microvascular endothelial cells (MEC), which are the main component of cells in BSCB. EGFR inhibition alleviates the disruption of BSCB and improves the functional recovery in rats following spinal cord injury (SCI). However, the biological mechanisms underlying EGFR activation mediating secondary damage after SCI remain unclear. Methods:An in vitro model of Oxygen and glucose deprivation/reoxygenation (OGD/R) induced BSCB damage and in vivo rat SCI model was employed to define the role of EGFR activation and its induced inflammatory injury during this pathological process in AS and MEC. AS and MEC were exposed to EGFR or p38 MAPK up-regulation in the presence and absence of EGFR inhibitor, p38 MAPK inhibitor, NF-κB inhibitor, and/or appropriate shRNA. RT-PCR, ELISA and western blotting were used for mRNA and protein expression analyses of TNF-α, iNOS, COX-2 and IL-1β. Immunohistochemical staining and confocal microscopy were used to demonstrate cellular EGFR activation and to investigate the expression of tight junction (TJ) protein (ZO-1 and occludin). Measurement of transendothelial electrical resistance (TEER) and transendothelial FITC-dextran permeability were used to measure permeability of BSCB in vitro, while Evans blue dye extravasation test and evaluation spinal cord edema were used to detect permeability of BSCB in vivo.Results:The expression of pEGFR was significantly increased in BSCB component cells (AS and MEC) after SCI and BSCB damage model. EGFR activation induced inflammation injury by upregulating the expression of TNF-α, iNOS, COX-2, and IL-1β and BSCB disruption with loss of TJ protein by downregulating the expression of ZO-1 and occludin in BSCB damage model and SCI rats. Moreover, EGFR or p38 activation leads to NF-κB nuclear translocation in primary AS and MEC after OGD/R. The EGFR inhibitor as well as shRNA against EGFR markedly attenuated pro-inflammatory factor excessive producing and loss of TJ protein, and activation of the EGFR/p38/NF-κB pathway. While, EGFR overexpression significantly increased the expression of TNF-α, iNOS, COX-2, and IL-1β and decrease the expression of ZO-1 and occludin, inducing activation of the EGFR/p38/NF-κB pathway in both AS and MEC. Conclusion:This study strongly suggests that EGFR activation in BSCB component cells after SCI and BSCB damage model mediates both upregulation of pro-inflammation expression and downregulation of TJ protein downregulation via the EGFR/p38/NF-κB pathway. These findings contribute to a better understanding of the biological mechanisms underlying BSCB disruption and secondary injury following SCI mediating by EGFR activation.

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Protein Degradome of Spinal Cord Injury: Biomarkers and Potential Therapeutic Targets

et al. 2020

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The microenvironment following oxygen glucose deprivation/re-oxygenation-induced BSCB damage in vitro

Cited by 7 publications

References 34 publications

Sodium Tanshinone IIA Silate Exerts Microcirculation Protective Effects against Spinal Cord Injury In Vitro and In Vivo

Sodium Tanshinone IIA Silate Exerts Microcirculation Protective Effects against Spinal Cord Injury In Vitro and In Vivo

Blocking the EGFR/p38/NF-κB Signal Pathway Alleviates Disruption of BSCB and Subsequent Inflammation After Spinal Cord Injury

Protein Degradome of Spinal Cord Injury: Biomarkers and Potential Therapeutic Targets

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