Zafirlukast protects blood-brain barrier integrity from ischemic brain injury

Publication date: Available online 6 December 2019Source: Chemico-Biological InteractionsAuthor(s): Chaosheng Zeng, Desheng Wang, Cong Chen, Lin Chen, Bocan Chen, Li Li, Min Chen, Huaijie XingAbstractStroke has been considered the second leading cause of death worldwide, and ischemic stroke accounts for the vast majority of stroke cases. Some of the main features of ischemic stroke are increased brain permeability, ischemia/reperfusion injury, oxidative stress, and acute inflammation. Antagonism of cysLT1R has been shown to provide cardiovascular and neural benefits. In the present study, we investigated the effects of the cysLT1R antagonist zafirlukast both in vivo and in vitro using a middle cerebral artery occlusion (MCAO) mouse model and human brain microvascular endothelial cells (HBMVECs). In vivo, we found that zafirlukast pretreatment could reduce MCAO-induced increased brain permeability by rescuing the expression levels of the tight junction proteins occludin and ZO-1. In vitro, we found that zafirlukast could suppress the increase in endothelial monolayer permeability induced by OGD/R via rescue of occludin and ZO-1 expression; additionally, we found that zafirlukast prevented OGD/R-induced degradation of the extracellular matrix via inhibition of MMP-2 and MMP-9 expression. Finally, we found that zafirlukast could also inhibit OGD/R-induced activation of the critical proinflammatory regulator NF-κB by preventing phosphorylation and nuclear translocation of p...
Source: Chemico Biological Interactions - Category: Biochemistry Source Type: research

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AbstractNeuroinflammation has been shown to exacerbate ischemic brain injury, and is considered as a prime target for the development of stroke therapies.Clinacanthus nutans Lindau (C. nutans) is widely used in traditional medicine for treating insect bites, viral infection and cancer, due largely to its anti-oxidative and anti-inflammatory properties. Recently, we reported that an ethanol extract from the leaf ofC. nutans could protect the brain against ischemia-triggered neuronal death and infarction. In order to further understand the molecular mechanism(s) for its beneficial effects, two experimental paradigms, namely,...
Source: NeuroMolecular Medicine - Category: Neurology Source Type: research
CONCLUSION: microRNA-421-3p prevents inflammatory response in cerebral ischemia/reperfusion injury through targeting YTHDF1 to inhibit p65 mRNA translation. These findings provide novel insights into understanding the molecular pathogenesis of cerebral I/R injury. PMID: 32890792 [PubMed - as supplied by publisher]
Source: International Immunopharmacology - Category: Allergy & Immunology Authors: Tags: Int Immunopharmacol Source Type: research
In this study, we investigated whether the expression of nuclear YAP in the astrocytes of rats increased significantly after middle cerebral artery occlusion (MCAO) and its effect on cerebral ischemic injury. We used XMU-MP-1 to trigger localization of YAP into the nucleus and found that XMU-MP-1 treatment decreased ischemia/stroke-induced brain injury including reduced neuronal death and reactive astrogliosis, and extenuated release of interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). Mechanically, XMU-MP-1 treatment suppressed the expression of phospho-STAT3 (P-STAT3...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research
Abstract The process of ischemia/reperfusion (IR) in ischemic stroke often leads to significant cell death and permanent neuronal damage. Safe and effective treatments are urgently needed to mitigate the damage caused by IR injury. The naturally occurring pleiotropic peptide phoenixin 14 (PNX-14) has recently come to light as a potential treatment for IR injury. In the present study, we examined the effects of PNX-14 on several key processes involved in ischemic injury, such as pro-inflammatory cytokine expression, oxidative stress, and the related cascade mediated through the toll-like receptor 4 (TLR4) pathway, ...
Source: Archives of Biochemistry and Biophysics - Category: Biochemistry Authors: Tags: Arch Biochem Biophys Source Type: research
AbstractIt is reported that baicalein can activate PI3K/AKT pathway, inhibit caspase activation and reduce cerebral infarct volume in middle cerebral artery occlusion (MCAO) rats. However, a caspase-independent mechanism initiated by poly (ADP-ribose) polymerase-1 (PARP-1) activation has been reported to make more contribution to cells death after ischemic stroke. In the present study, we established a cerebral ischemia/reperfusion (I/R) rat model through middle cerebral artery occlusion following reperfusion to investigate the mechanisms of ischemic tissue recovery following baicalein treatment. The data showed that baica...
Source: Apoptosis - Category: Molecular Biology Source Type: research
Adiponectin peptide alleviates oxidative stress and NLRP3 inflammasome activation after cerebral ischemia-reperfusion injury by regulating AMPK/GSK-3β. Exp Neurol. 2020 Apr 07;:113302 Authors: Liu H, Wu X, Luo J, Zhao L, Li X, Guo H, Bai H, Cui W, Guo W, Feng D, Qu Y Abstract The effects of current treatment strategies for ischemic stroke are weakened by ischemia-reperfusion (I/R) injury. Effective treatments targeting I/R injury are still insufficient. Adiponectin (APN), a fat-derived hormone, has a wide range of antioxidative and anti-inflammatory effects. However, the application of APN to the...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research
Mammalian mitochondrial permeability transition pore (MPTP), across the inner and outer membranes of mitochondria, is a nonspecific channel for signal transduction or material transfer between mitochondrial matrix and cytoplasm such as maintenance of Ca2+ homeostasis, regulation of oxidative stress signals, and protein translocation evoked by some of stimuli. Continuous MPTP opening has been proved to stimulate neuronal apoptosis in ischemic stroke. Meanwhile, inhibition of MPTP overopening-induced apoptosis has shown excellent efficacy in the treatment of ischemic stroke. Among of which, the potential molecular mechanisms...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
ConclusionTGs are the main active components of C. deserticola against MCAO/R-induced cerebral injury, and protection is mainly via the Nrf-2/Keap-1 pathway.
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Abstract A series of 1,2,4-triazole derivatives 1-14 was synthesized to investigate their neuroprotective effects and mechanisms of action. Compounds 5-11 noticeably protected PC12 cells from the cytotoxicity of H2O2 or sodium nitroprusside (SNP). Compound 11 was the most effective derivative. Compound 11 chelated Fe (II) iron, scavenged reactive oxygen species (ROS), and restored the mitochondrial membrane potential (MMP). Moreover, it enhanced the activity of the antioxidant defense system by increasing the serum level of superoxide dismutase (SOD) and promoting the nuclear translocation of nuclear factor e...
Source: European Journal of Medicinal Chemistry - Category: Chemistry Authors: Tags: Eur J Med Chem Source Type: research
Publication date: Available online 8 January 2020Source: Life SciencesAuthor(s): Guoyuan Pan, Lingqin Jin, Weimin Shen, Jieqiong Zhang, Juanjuan Pan, Jingyan Cheng, Qingfeng Xie, Quan Hu, Shamin Wu, Hongmei Zhang, Xiang ChenAbstractAimsTreadmill exercise is a beneficial treatment following childhood stroke. Thus, studies focusing on the neuroprotective mechanism of exercise training during postischemic treatment in children with ischemic stroke are urgently needed. We evaluated the effects of treadmill exercise on autophagy after cerebral ischemia in young rats.Main methodsRats (23–25 days old) underwent cerebral i...
Source: Life Sciences - Category: Biology Source Type: research
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