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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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
AbstractSpreading depolarization is observed as a large negative shift of the direct current potential, swelling of neuronal somas, and dendritic beading in the brain ’s gray matter and represents a state of a potentially reversible mass injury. Its hallmark is the abrupt, massive ion translocation between intraneuronal and extracellular compartment that causes water uptake (= cytotoxic edema) and massive glutamate release. Dependent on the tissue’s energy st atus, spreading depolarization can co-occur with different depression or silencing patterns of spontaneous activity. In adequately supplied tissue, spread...
Source: AGE - Category: Geriatrics Source Type: research
Abstract Stroke 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 vi...
Source: Chemico-Biological Interactions - Category: Molecular Biology Authors: Tags: Chem Biol Interact Source Type: research
In conclusion, these results demonstrate that Ropinirole treatment is beneficial in preserving the mitochondrial functions that are altered in cerebral ischemic injury and thus can help in defining better therapies. PMID: 31816341 [PubMed - as supplied by publisher]
Source: Neurotoxicology - Category: Neurology Authors: Tags: Neurotoxicology Source Type: research
Abstract Cerebral ischemia-reperfusion injury is a complex pathophysiological process. Poly(ADP-ribose) (PAR) polymerase-1 (PARP-1)/apoptosis-inducing factor (AIF) signaling pathway-mediated apoptosis is one of the non-caspase-dependent cell death programs that are widely present in neurological diseases such as stroke. In our study, we aimed to conduct further research on the effects of Gualou Guizhi decoction (GLGZD) on the PARP-1/AIF signaling pathway in cell apoptosis after ischemia-reperfusion injury caused by middle cerebral artery occlusion (MCAO). The results showed that GLGZD administration for 7 day...
Source: Neurochemical Research - Category: Neuroscience Authors: Tags: Neurochem Res Source Type: research
CONCLUSIONS The results indicated that biochanin A protected the brain against ischemic injury in rats by anti-oxidative and anti-inflammatory actions. The activation of the Nrf2 pathway and the inhibition of the NF-kappaB pathway may contribute to the neuroprotective effects of biochanin A. PMID: 31767824 [PubMed - in process]
Source: Medical Science Monitor - Category: Research Tags: Med Sci Monit Source Type: research
In this study, we explored the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) in the process of BBR-induced inhibition of HMGB1 in ischemic brain. Before the 60-min MCAO surgery, the mice were pretreated with BBR (50 mg· kg-1 per day, ig) for 14 days or ICV injected with specific lentiviral vector or shRNA. We showed that MCAO caused marked increase in the expression Malat1 and HMGB1 in the ipsilateral cortex, which was significantly attenuated by pretreatment with BBR. Knockdown of Malat1 attenuated the inflammatory injury after brain ischemia, whereas overexpression of...
Source: Acta Pharmacologica Sinica - Category: Drugs & Pharmacology Authors: Tags: Acta Pharmacol Sin Source Type: research
In conclusion, we found that Botch exerts neuroprotective effects via antagonizing the maturation of Notch1-induced neuronal injury and neuroinflammation, which may provide insights into novel therapeutic targets for the treatment of I/R injury. PMID: 31377404 [PubMed - as supplied by publisher]
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research
AbstractCerebral ischemic stroke is a severe disease afflicting people worldwide. Phytochemicals play a pivotal role in the discovery of novel therapeutic approaches for the prevention of ischemic stroke. In our continual search for bioactive natural products for the treatment of ischemic stroke, we have evaluated the protective effects of theaflavic acid (TFA) from black tea using PC12 cells injured by oxygen and glucose deprivation/restoration (OGD/R), and investigated the possible mechanisms. The results showed that TFA can protect PC12 cells against OGD/R through increasing cell viability and decreasing intracellular l...
Source: Journal of Natural Medicines - Category: Drugs & Pharmacology Source Type: research
Publication date: September 2019Source: Biomedicine &Pharmacotherapy, Volume 117Author(s): Shilun Yang, Haigang Wang, Yinglin Yang, Rui Wang, Yuehua Wang, Chunfu Wu, Guanhua DuAbstractIschemic stroke is a cerebrovascular disease with high morbidity, high mortality, and high disability, representing a serious threat to human life and health. Clinically, the extensive injury caused by ischemic stroke results from ischemia-reperfusion (I/R) injury thrombolytic treatment. However, there are few reports on the use of medications in the subacute stage of cerebral I/R. Baicalein (5,6,7-trihydroxyflavone) is a biologically act...
Source: Biomedicine and Pharmacotherapy - Category: Drugs & Pharmacology Source Type: research
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