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Stroke reperfusion injury

Wei-Ming He, Li Ying-Fu, He Wang, Yu-Ping Peng
Development of effective therapeutics and treatment strategy to promote recovery after cerebral ischemia-reperfusion injury necessitates further understandings of the complex pathophysiology of ischemic stroke. Given that α5-GABAA R inhibition has been shown to be involved in functional recovery after stroke, the present study was designed to evaluate the effects of treatment timing of α5 GABAA R inhibition on post-middle cerebral artery occlusion (MCAO) functional recovery. To this end, we examined the effects of L655,708 (α5 GABAA R inverse agonist) treatment at 3 or 7 days post-ischemia on apoptosis and neurogenesis in the peri-infarct region, brain infarction size, as well as modified neurological severity score (mNSS) and rotarod test time in rats...
February 19, 2019: Scientific Reports
Alaa Elkordy, Sherif Rashad, Heba Shehabeldeen, Eikan Mishima, Kuniyasu Niizuma, Takaaki Abe, Teiji Tominaga
The disruption of appropriate cellular stress responses is implicated in the pathogenesis of different neurological disorders including ischemic injury. Early diagnosis and treatment are often associated with better prognosis in ischemic stroke patients. Thus, there is an urgent need to improve the speed and accuracy of stroke diagnosis by developing highly sensitive stroke biomarkers. We recently reported that transfer RNA (tRNA) was involved in cell stress response pathways. Under cell stress conditions, mature tRNA is cleaved by a specific ribonuclease, angiogenin, generating tRNA-derived stress-induced RNA (tiRNA)...
February 16, 2019: Brain Research
Rong Zhang, Weipin Zhou, Zhijun Yu, Ling Yang, Guangqi Liu, Haotian Yu, Qianyi Zhou, Zhenli Min, Chunxiang Zhang, Qingming Wu, Xia-Min Hu, Qiong Yuan
Brain stroke is one of the leading causes of death worldwide. We explored a potential stroke-related role for a newly found microRNA, miR-1247-3p, and one of its target genes, caspase-2, predicted by TargetScanVert. In the present study, we found that miR-1247-3p was downregulated during ischemia/reperfusion (I/R) and that LV-miR-1247-3p overexpression attenuated brain impairment induced by I/R. Similar results were observed in neuro2a (N2a) cells treated with oxygen-glucose deprivation/reoxygenation (OGD/R)...
February 16, 2019: Brain Research
N R Bonetti, C Diaz-Cañestro, L Liberale, M Crucet, A Akhmedov, M Merlini, M F Reiner, S Gobbato, S Stivala, G Kollias, F Ruschitzka, T F Lüscher, J H Beer, G G Camici
Rheumatoid Arthritis (RA) is a chronic inflammatory disorder where incidence and severity of myocardial infarction are increased. Data on the incidence and outcome of stroke are conflicting. Thus, we investigated outcome after Ischemia/Reperfusion (I/R) brain injury in a mouse model of RA and assessed for the role of the tumour necrosis factor-α (TNF-α) inhibitor Infliximab herein. We used a TNF-α reliant mouse model of RA. RA and wildtype (WT) animals were treated with vehicle (RA/WT) or Infliximab (RA Infliximab) for 4 weeks, before undergoing I/R brain injury...
February 18, 2019: Scientific Reports
Abhijit Nirwane, Jessica Johnson, Benjamin Nguyen, Jeffrey H Miner, Yao Yao
At the blood-brain barrier (BBB), laminin-α5 is predominantly synthesized by endothelial cells and mural cells. Endothelial laminin-α5 is dispensable for BBB maintenance under homeostatic conditions but inhibits inflammatory cell extravasation in pathological conditions. Whether mural cell-derived laminin-α5 is involved in vascular integrity regulation, however, remains unknown. To answer this question, we generated transgenic mice with laminin-α5 deficiency in mural cells (α5-PKO). Under homeostatic conditions, no defects in BBB integrity and cerebral blood flow (CBF) were observed in α5-PKO mice, suggesting that mural cell-derived laminin-α5 is dispensable for BBB maintenance and CBF regulation under homeostatic conditions...
February 18, 2019: Acta Neuropathologica Communications
Yanhui Yu, Xiuhui Zhang, Zhengmin Han, Weili Zhao, Limin Zhang
Rodent focal ischemia models are widely used to mimic and examine human strokes. To the best of our knowledge, no investigation has systematically examined the expression changes of microRNA (miR)-449a and Amphiregulin (AREG) as well as their biological relationship during middle cerebral artery occlusion (MCAO) and oxygen and glucose deprivation/reperfusion (OGD/R). The present study examined the histological and behavioral outcomes of MCAO and the function of miR-449a and AREG in cerebral ischemic injury...
February 18, 2019: Metabolic Brain Disease
Jiamei Shen, Radhika Rastogi, Xiaokun Geng, Yuchuan Ding
Nicotinamide adenine dinucleotide phosphate oxidase (NOX) is a multisubunit enzyme complex that utilizes nicotinamide adenine dinucleotide phosphate to produce superoxide anions and other reactive oxygen species. Under normal circumstances, reactive oxygen species mediate a number of important cellular functions, including the facilitation of adaptive immunity. In pathogenic circumstances, however, excess reactive oxygen species generated by NOX promotes apoptotic cell death. In ischemic stroke, in particular, it has been shown that both NOX activation and derangements in glucose metabolism result in increased apoptosis...
June 2019: Neural Regeneration Research
Konrad A Szychowski, Jan Gmiński
The products of elastin degradation, namely elastin-derived peptides (EDPs), are detectable in the cerebrospinal fluid of healthy individuals and in patients after ischemic stroke, and their number increases with age. Depending on their concentrations, both nitric oxide (NO) and reactive oxygen species (ROS) take part either in myocardial ischemia reperfusion injury or in neurovascular protection after ischemic stroke. The aim of our study was to determine the impact of VGVAPG peptide on ROS and NO production and expression of endothelial nitric oxide synthase (eNos), inducible nitric oxide synthase (iNos) and neuronal nitric oxide synthase (nNos) in mouse cortical astrocytes in vitro...
February 13, 2019: Neurochemical Research
Hui Wang, Wei Wei, Xiaobing Lan, Ning Liu, Yuxiang Li, Hanxiang Ma, Tao Sun, Xiaodong Peng, Chunlin Zhuang, Jian Qiang Yu
Oxidative stress plays a vital role in the development of cerebral ischemic/reperfusion (I/R). Targeting oxidative stress is proposed to be an effective strategy to treat cerebral I/R injury. Gentiana macrophylla Pall is reported to have potential protective effect against stroke. Swertiamarin (Swe), an active secoiridoid glycoside compound isolated from Gentiana macrophylla Pall, has been reported to possess the antioxidative potential. This study is to explore whether Swe could prevent brain from I/R injury and the related mechanisms of oxidative stress is also elucidated using mice middle cerebral artery occlusion (MCAO) model and primary hippocampal neurons oxygen-glucose deprivation/reperfusion (OGD/R) model...
February 12, 2019: ACS Chemical Neuroscience
Qingqing Dai, Shujuan Li, Ting Liu, Jiayin Zheng, Song Han, Aijuan Qu, Junfa Li
We previously reported that astrocytes are the main sources of interleukin (IL)-17A production that could aggravate neuronal injuries in ischemic stroke. However, the effects of IL-17A on ischemic astrocytes themselves and the underlying molecular mechanism are still unclear. In this study, we found that recombinant mouse (rm) IL-17A could significantly (P < 0.05 or <0.001) alleviate 1-hour oxygen-glucose deprivation (OGD)/reoxygenation (R) 24-hour-induced ischemic injuries in cortical astrocytes with a dose-dependent manner (n = 6 per group)...
February 11, 2019: Journal of Cellular Biochemistry
Yang Li, Dongcheng Feng, Zhanyu Wang, Yan Zhao, Ruimin Sun, Donghai Tian, Deshun Liu, Feng Zhang, Shili Ning, Jihong Yao, Xiaofeng Tian
Ferroptosis is a recently identified form of regulated cell death defined by the iron-dependent accumulation of lipid reactive oxygen species. Ferroptosis has been studied in various diseases such as cancer, Parkinson's disease, and stroke. However, the exact function and mechanism of ferroptosis in ischemia/reperfusion (I/R) injury, especially in the intestine, remains unknown. Considering the unique conditions required for ferroptosis, we hypothesize that ischemia promotes ferroptosis immediately after intestinal reperfusion...
February 8, 2019: Cell Death and Differentiation
Boris M Baranovski, Ronen Schuster, Omer Nisim, Ido Brami, Yotam Lior, Eli C Lewis
Alpha-1 antitrypsin deficiency (AATD) is a genetic disorder which most commonly manifests as pulmonary emphysema. Accordingly, alpha-1 antitrypsin (AAT) augmentation therapy aims to reduce the progression of emphysema, as achieved by life-long weekly slow-drip infusions of plasma-derived affinity-purified human AAT. However, not all AATD patients will receive this therapy, due to either lack of medical coverage or low patient compliance. To circumvent these limitations, attempts are being made to develop lung-directed therapies, including inhaled AAT and locally-delivered AAT gene therapy...
September 19, 2018: Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation
Won Ho Kim, Hye-Won Oh, Seong-Mi Yang, Je Hyuk Yu, Hyung-Chul Lee, Chul-Woo Jung, Kyung-Suk Suh, Kook Hyun Lee
BACKGROUND: Acute kidney injury (AKI) after living donor liver transplantation (LDLT) is associated with increased mortality. We sought to identify associations between intraoperative hemodynamic variables and postoperative AKI. METHODS: We retrospectively reviewed 734 cases of LDLT. Intraoperative hemodynamic variables of systemic and pulmonary arterial pressure, central venous pressure (CVP), and pulmonary artery catheter-derived parameters including mixed venous oxygen saturation (SvO2), right ventricular end-diastolic volume (RVEDV), stroke volume, systemic vascular resistance, right ventricular ejection fraction, and stroke work index were collected...
January 30, 2019: Transplantation
Raheleh Gholamzadeh, Mehdi Eskandari, Mohammad Reza Bigdeli, Hossein Mostafavi
Introduction: Brain Ichemic-Reperfusion Injury (IRI) activates different pathophysiological processes. It also changes physiological parameters such as Blood Glucose (BG) level. An increase in BG after stroke is associated with poor clinical outcomes. Erythropoietin has been shown to be effective on both reducing inflammation and BG level. Therefore, in this study the erythropoietin pretreatment effect on BG and its relationship with inflammatory markers after brain IRI was investigated...
September 2018: Basic and Clinical Neuroscience
Si-Jia Zhang, Rong-Liang Wang, Hai-Ping Zhao, Zhen Tao, Jin-Cheng Li, Fei Ju, Zi-Ping Han, Qing-Feng Ma, Ping Liu, Shu-Bei Ma, Guo-Dong Cao, Yu-Min Luo
Previously study has proved the non-erythropoietic mutant erythropoietin (MEPO) exerted neuroprotective effects against ischemic cerebral injury, with an efficacy similar to that of wild-type EPO. This study investigates its effects on neurogenesis, angiogenesis, and gliogenesis in cerebral ischemic mice. Male C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO) and reperfusion. EPO (5000 U/kg), MEPO (5000 U/kg) or equal volume of normal saline was injected intraperitoneally. Neurological function was evaluated by Rota-rod test, Neurological severity scores (NSS) and Adhesive removal test...
February 2, 2019: European Journal of Pharmacology
Fatemeh Forouzanfar, Mana Shojapour, Samira Asgharzade, Elham Amini
Stroke continues to be a major cause of death and disability worldwide. In this respect, the most important mechanisms underlying stroke pathophysiology are inflammatory pathways, oxidative stress, as well as apoptosis. Accordingly, miRNAs are considered as non-coding endogenous RNA molecules interacting with their target mRNAs to inhibit mRNA translation or reduce its transcription. Studies in this domain have similarly shown that miRNAs are strongly associated with coronary artery disease and correspondingly contribute to the brain ischemia molecular processes...
February 3, 2019: CNS & Neurological Disorders Drug Targets
Hang Xu, Tianlong Liu, Wenjun Wang, Ning Su, Liudi Yang, Zhifu Yang, Fang Dou, Jia Cui, Fei Fei, Jing Ma, Aidong Wen, Yi Ding
Ischemic stroke is a common cerebrovascular disease with high morbidity and mortality worldwide. However, treatment options for reducing cerebral ischemia-reperfusion injury (CIRI) are limited. Gallic acid (GA) as a plant polyphenol has been used to fight against CIRI. But its pharmacokinetic properties such as low absorption, poor bioavailability and quick elimination have negative effects on its clinical application. To strengthen its potency, a delivery system of GA-loaded o-carboxymethyl chitosan nanoparticle (GA-NP) was synthesized in our study...
February 2, 2019: Rejuvenation Research
Rui Liu, Xin-Yu Liao, Meng-Xian Pan, Jun-Chun Tang, Song-Feng Chen, Ya Zhang, Pei-Xin Lu, Long J Lu, Ying-Ying Zou, Xing-Ping Qin, Li-Hong Bu, Qi Wan
Glycine is a simple nonessential amino acid known to have neuroprotective properties. Treatment with glycine results in reduced infarct volume of the brain, neurologic function scores, and neuronal and microglial death in ischemic stroke injury. Neuroinflammation has been considered a major contributor to cerebral ischemia-induced brain damage. However, the role of glycine in neuroinflammation following ischemic stroke is unclear. The present study aimed to determine whether neuroinflammation is involved in the neuroprotective effects of glycine in cerebral ischemia injury...
February 1, 2019: Journal of Immunology: Official Journal of the American Association of Immunologists
Jialin Duan, Jia Cui, Zhifu Yang, Chao Guo, Jinyi Cao, Miaomiao Xi, Yan Weng, Ying Yin, Yanhua Wang, Guo Wei, Boling Qiao, Aidong Wen
BACKGROUND: Previous studies had showed that Apelin 13 could protect against apoptosis induced by ischemic/reperfusion (I/R). However, the mechanisms whereby Apelin 13 protected brain I/R remained to be elucidated. The present study was designed to determine whether Apelin 13 provided protection through AMPK/GSK-3β/Nrf2 pathway. METHODS: In vivo, the I/R model was induced and Apelin 13 was given intracerebroventricularly 15 min before reperfusion. The neurobehavioral scores, infarction volumes, and some cytokines in the brain were measured...
February 1, 2019: Journal of Neuroinflammation
Umadevi V Wesley, Vijesh J Bhute, James F Hatcher, Sean P Palecek, Robert J Dempsey
Metabolic dysfunction impacts stroke incidence and outcome. However, the intricate association between altered metabolic program due to aging, and focal ischemia in brain, circulation, and peripheral organs is not completely elucidated. Here we identified locally and systemically altered metabolites in brain, liver, and plasma as a result of normal aging, ischemic-stroke, and extended time of reperfusion injury. Comprehensive quantitative metabolic profiling was carried out using nuclear magnetic resonance spectroscopy...
January 29, 2019: Neurochemistry International
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