N-Butylphthalide Alleviates Blood–Brain Barrier Impairment in Rats Exposed to Carbon Monoxide

Bi, Minghong; Zhang, Mingwei; Guo, Dadong; Bi, Weikang; Liu, Bin; Zou, Yong; Li, Qin

doi:10.3389/fphar.2016.00394

Cited by 24 publications

(18 citation statements)

References 41 publications

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“…Our observations were in good agreement with the findings of a previous investigation in which ZO-1 was expressed both in the BBB and the non-vessel barrier. [20] Although ZO-1 is not a specific TJ marker, ZO-1 is an important component protein of TJs and an important TJ regulator, which plays an important role in the maintenance of cell polarity, cytoskeleton formation, TJ localization, and paracellular barrier. ZO-1 is closely related to BBB permeability.…”

Section: Discussionmentioning

confidence: 99%

DL-3-n-butylphthalide protects the blood-brain barrier against ischemia/hypoxia injury via upregulation of tight junction proteins

Xing

Wang

et al. 2019

Chinese Medical Journal

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Background: The increased permeability of the blood-brain barrier (BBB) induced by ischemia/hypoxia is generally correlated with alteration of tight junctions (TJs). DL-3-n-butylphthalide (NBP) has been shown to exert neuroprotective effects after ischemic injury. However, few studies have assessed the correlation between NBP and TJs. This study aimed to investigate the potential effect of NBP on the TJ proteins claudin-5, zonula occludens-1 (ZO-1), and occludin during brain ischemia. Methods: A chronic cerebral hypoperfusion (CCH) Sprague-Dawley rat model was established, and NBP (20, 40, or 80 mg/kg, gavage, once a day) treatment was performed for 14 days. NBP (0.1 or 1.0 μmol/L) pre-treatment was applied to an in vitro hypoxia microvascular endothelial cell model (1% O 2 , 24 h). BBB permeability was assessed by performing the Evans blue assay. The expressions and localization of claudin-5, ZO-1, occludin, phosphorylated/total protein kinase B (p-Akt/Akt), phosphorylated/total glycogen synthase kinase 3β (GSK-3β)/GSK-3β, and β-catenin/β-actin were evaluated by Western blotting or immunofluorescence. Reactive oxygen species (ROS) generation was measured by flow cytometry analysis. TJ ultrastructure was observed by transmission electron microscopy. Results: In CCH rats, treatment with 40 and 80 mg/kg NBP decreased the Evans blue content in brain tissue (9.0 ± 0.9 μg/g vs. 12.3 ± 1.9 μg/g, P = 0.005; 6.7 ± 0.6 μg/g vs. 12.3 ± 1.9 μg/g, P < 0.01), increased the expression of claudin-5 (0.79 ± 0.08 vs. 0.41 ± 0.06, P < 0.01; 0.97 ± 0.07 vs. 0.41 ± 0.06, P < 0.01), and elevated the ZO-1 protein level ( P < 0.05) in brain microvascular segments in a dose-dependent manner in comparison with the corresponding values in the model group. There was no significant difference in occludin expression ( P > 0.05). In the hypoxia cell model, NBP pre-treatment improved TJ ultrastructure, decreased intracellular ROS level, and increased the expression of claudin-5 ( P < 0.01) and ZO-1 ( P < 0.01) in comparison with the corresponding values in the hypoxia group. NBP treatment also elevated the relative expression levels of p-Akt/Akt, p-GSK-3β/GSK-3β, and β-catenin/β-actin in comparison with the corresponding values in the hypoxia group (all P < 0.05). Conclusion: NBP improves the barrier function of BBB against ischemic injury by upregulating the expression of TJ proteins, possibly by reducing oxidative stress and activating the Akt/GSK-3β/β-catenin signaling pathway.

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Section: Discussionmentioning

confidence: 99%

DL-3-n-butylphthalide protects the blood-brain barrier against ischemia/hypoxia injury via upregulation of tight junction proteins

Xing

Wang

et al. 2019

Chinese Medical Journal

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“…The BBB permeability can be affected by a plethora of factors such as viral and bacterial infection, traumatic brain injury, poisoning, or hypertension . Interestingly, it seems that factors from the gut microbiota can also affect BBB permeability, because germ‐free or antibiotic‐treated mice show an increased BBB permeability and altered expression of tight junction proteins .…”

Section: Introductionmentioning

confidence: 99%

The role of CNS macrophages in streptococcal meningoencephalitis

Gres

Kolter

Erny

et al. 2019

Journal of Leukocyte Biology

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In the healthy brain, microglia and other CNS macrophages are the most abundant immune cell type. Thus, they form the natural immune cell interface with streptococci, which are the leading cause of bacterial meningitis and encephalitis in infants and young children. In homeostasis, the blood-brain barrier allows for very limited access of immune cells circulating in the periphery. During bacterial meningoencephalitis, however, origin and fate of CNS macrophages are massively altered. This review summarizes the emerging knowledge on the sequence of reciprocal events between streptococci and CNS macrophages leading to host resistance, acute inflammation, changes in resident innate immune cells of the brain, and long-term neuronal damage. K E Y W O R D S meningitis, microglia, Streptococcus agalactiae, Streptococcus pneumoniae [The copyright line for this article was changed on 25 February 2019 after original online publication] of events can transiently severely perturb the separation of the CNS and the peripheral immune system. Thereby, long-term consequences for neurodevelopment might ensue.

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“…In experimental stroke models, NBP was reported to possess anti-platelet [21] and anti-apoptosis [22] activities, as well as the promotion of neural regeneration [23, 24]. In addition, NBP treatment preserved cerebral blood flow [25, 26], improved BBB integrity [26] and reduced cerebrovascular thrombosis [25]. However, the mechanisms underlying this process remain unknown, and few studies have focused on the inflammatory state of the endothelium and vascular inflammation.…”

mentioning

confidence: 99%

Dl-3-n-butylphthalide Reduces Neurovascular Inflammation and Ischemic Brain Injury in Mice

Yang¹,

Ai²,

Li³

et al. 2019

Aging and disease

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Dl-3-n-butylphthalide (NBP) is a synthetic compound that has been approved for the treatment of ischemic stroke in China. The mechanisms underlying the treatment efficacy of NBP have been reported in multiple studies and remain controversial. Here, we show that NBP treatment attenuated ischemic brain injury in mice subjected to transient middle cerebral artery occlusion or photothrombosis-induced permanent cerebral ischemia. NBP induced downregulation of intercellular adhesion molecule 1 and protease-activated receptor 1 in cerebrovascular endothelial cells after cerebral ischemia and reperfusion. This effect was associated with the reduced brain infiltration of myeloid cells and improved cerebral blood flow after reperfusion. The beneficial effects of NBP were diminished in mice subjected to the depletion of Gr1 + myeloid cells before brain ischemia. Therefore, the restriction of neurovascular inflammation is a key mode of action for NBP in ischemic stroke.

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N-Butylphthalide Alleviates Blood–Brain Barrier Impairment in Rats Exposed to Carbon Monoxide

Cited by 24 publications

References 41 publications

DL-3-n-butylphthalide protects the blood-brain barrier against ischemia/hypoxia injury via upregulation of tight junction proteins

DL-3-n-butylphthalide protects the blood-brain barrier against ischemia/hypoxia injury via upregulation of tight junction proteins

The role of CNS macrophages in streptococcal meningoencephalitis

Dl-3-n-butylphthalide Reduces Neurovascular Inflammation and Ischemic Brain Injury in Mice

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