Baicalin reduces the permeability of the blood–brain barrier during hypoxia in vitro by increasing the expression of tight junction proteins in brain microvascular endothelial cells

Zhu, Haiyan; Wang, Zhiyao; Xing, Yanwei; Gao, Yonghong; Ma, Tao; Lou, Lixia; Lou, Jinning; Gao, Ying; Shuo-ren, Wang; Wang, Yongyan

doi:10.1016/j.jep.2011.08.063

Cited by 80 publications

(55 citation statements)

References 26 publications

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“…Cerebral ischemia (or stroke) induces dramatic cerebral injury and a massive barrier disruption. Although different studies brought some crucial information on how hypoxic stress induces barrier disruption (Bauer et al, 2010;Vogel et al, 2007;Yan et al, 2011;Zhu et al, 2011), the mechanisms remain largely unclear. Oxidative stress is defined as an imbalance between cellular pro-oxidants and antioxidants, resulting in excessive generation of reactive free radicals in the central nervous system (Mariani et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

Involvement of oxidative stress in hypoxia-induced blood–brain barrier breakdown

Ahmad

Gassmann

Ogunshola

2012

Microvascular Research

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The blood-brain barrier (BBB) is a cellular barrier formed by specialized brain endothelial cells under the influence of astrocytes and pericytes. Among the several stress factors known to induce BBB breakdown, hypoxia is probably the most represented but also the least understood. Recent evidence of oxidative stress occurring during hypoxia/ischemia situation raises its possible contribution to barrier breakdown. In this study, we investigated the relevance of oxidative stress in hypoxia-induced barrier disruption. Prolonged hypoxic exposure induced radical oxygen species (ROS) formation and induced glutathione oxidation. Such effects were accentuated under extreme O(2) deprived environment. Prooxidant treatment significantly disrupted barrier function under normal conditions, whereas anti-oxidant treatment contributed to maintain better barrier function and cell survival in an O(2)-reduced environment. In addition, the endothelial response to oxidative stress appeared modulated by the presence of astrocytes and pericytes, thus explaining some of the beneficial contribution of these cells as previously described. Taken together, this study highlights the importance of oxidative stress signaling at the barrier. In addition, cells of the neurovascular compartment differentially modulate ROS levels and also regulate barrier function. Thus, use of radical scavengers may be useful to support barrier function following stroke injury.

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Section: Introductionmentioning

confidence: 99%

Involvement of oxidative stress in hypoxia-induced blood–brain barrier breakdown

Ahmad

Gassmann

Ogunshola

2012

Microvascular Research

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“…It has been reported that alteration of TJ protein expression plays an important role in endothelial barrier disruption induced by hypoxia [18,19]. Therefore, to determine whether the augmentation of hypoxia-induced endothelial barrier dysfunction by HIF-1α overexpression is accompanied by the changed expression of TJ proteins, we analyzed the expression of TJ proteins ZO-1 and occludin by immunoblot assay.…”

Section: Resultsmentioning

confidence: 99%

“…However, conflicting reports have raised debates on the exact role of altered tight junction protein expression in endothelial barrier dysfunction caused by hypoxia. For instance, previous studies have shown that the reduced expression of ZO-1 and claudin-5 is involved in endothelial barrier disruption caused by hypoxia [18,19]. On the contrary increase of occludin expression has been reported to be associated with the hypoxia-induced endothelial barrier dysfunction [44].…”

Section: Discussionmentioning

confidence: 99%

Overexpression of Hypoxia-Inducible Factor-1a Exacerbates Endothelial Barrier Dysfunction Induced by Hypoxia

Wang

Qi²,

Sun³

et al. 2013

Cell Physiol Biochem

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Background/Aims: The mechanisms involved in endothelial barrier dysfunction induced by hypoxia are incompletely understood. There is debate about the role of hypoxia-inducible factor-1α (HIF-1α) in endothelial barrier disruption. The aim of this study was to investigate the effect of genetic overexpression of HIF-1α on barrier function and the underlying mechanisms in hypoxic endothelial cells. Methods: The plasmid pcDNA3.1/V5-His-HIF-1α was stably transfected into human endothelial cells. The cells were exposed to normoxia or hypoxia. The mRNA and protein expressions of HIF-1α were detected by RT-PCR and Western blot respectively. The barrier function was assessed by measuring the transendothelial electrical resistance (TER). The Western blot analysis was used to determine the protein expression of glucose transporter-1 (GLUT-1), zonular occludens-1 (ZO-1), occludin, and myosin light chain kinase (MLCK) in endothelial cells. The mRNA expression of proinflammatory cytokines was detected by qRT-PCR. Results: Genetic overexpression of HIF-1α significantly increased the mRNA and protein expression of HIF-1α in endothelial cells. The overexpression of HIF-1α enhanced the hypoxia-induced increase of HIF-1α and GLUT-1 protein expression. HIF-1α overexpression not only exacerbated hypoxia-induced endothelial barrier dysfunction but also augmented hypoxia-induced up-regulation of MLCK protein expression. HIF-1α overexpression also enhanced IL-1β, IL-6 and TNF-α mRNA expression. Conclusion: We provide evidence that genetic overexpression of HIF-1α aggravates the hypoxia-induced endothelial barrier dysfunction via enhancing the up-regulation of MLCK protein expression caused by hypoxia, suggesting a potential role for HIF-1α in the pathogenesis of endothelial barrier dysfunction in hypoxia.

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“…For example, it has been reported that baicalin isolated from Scutellaria baicalensis reduces the permeability of the blood-brain barrier by increasing expression of claudin-5 and zonular occludens-1 TJ proteins in the endothelial cells of brain microvessels. 26) That study suggested that baicalin could suppress the inflammatory reaction and tissue injury in the brain by reinforcing the blood-brain barrier. Our study showed that the trachelogenin from TCE could inhibit allergen permeation by enhancing the effect of occludin on intestinal barrier function, and that the effect of trachelogenin could be applied not only in intestinal epithelial cells (GI system) but also in other endothelial cells (respiratory and circulatory systems).…”

Section: Discussionmentioning

confidence: 99%

Enhancing Effect of Trachelogenin from <i>Trachelospermi caulis</i> Extract on Intestinal Barrier Function

Shin

Bae

See

et al. 2015

Biological & Pharmaceutical Bulletin

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Baicalin reduces the permeability of the blood–brain barrier during hypoxia in vitro by increasing the expression of tight junction proteins in brain microvascular endothelial cells

Cited by 80 publications

References 26 publications

Involvement of oxidative stress in hypoxia-induced blood–brain barrier breakdown

Involvement of oxidative stress in hypoxia-induced blood–brain barrier breakdown

Overexpression of Hypoxia-Inducible Factor-1a Exacerbates Endothelial Barrier Dysfunction Induced by Hypoxia

Enhancing Effect of Trachelogenin from <i>Trachelospermi caulis</i> Extract on Intestinal Barrier Function

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