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ischemic stroke inflammation

Alina Mihaela Leustean, Manuela Ciocoiu, Anca Sava, Claudia Florida Costea, Mariana Floria, Claudia Cristina Tarniceriu, Daniela Maria Tanase
The prevalence of diabetes is steadily rising, and once it occurs, it can cause multiple complications with a negative impact on the whole organism. Complications of diabetes may be macrovascular: such as stroke and ischemic heart disease as well as peripheral vascular and microvascular diseases-retinopathy, nephropathy, and neuropathy. Key factors that cause cardiovascular disease in people with diabetes include hyperglycemia, dyslipidemia, obesity, insulin resistance, inflammation, hypertension, autonomic dysfunction, and decreased vascular response capacity...
2018: Journal of Diabetes Research
Munehisa Shimamura, Hironori Nakagami, Hideo Shimizu, Hideyuki Mukai, Ryosuke Watanabe, Takeshi Okuzono, Tomohiro Kawano, Yuka Ikeda, Hiroki Hayashi, Shota Yoshida, Nan Ju, Hideki Mochizuki, Ryuichi Morishita
Although the regulation of post-ischemic inflammation is an important strategy to treat ischemic stroke, all clinical trials have failed to show its efficacy. To solve the problem, we previously developed a novel partial peptide of RANKL, microglial healing peptide 1 (MHP1), which could reduce ischemic injury by inhibiting Toll-like receptor (TLR) induced inflammation. However, optimization of the peptide was necessary to increase the stability and efficacies for clinical use. According to information gathered through HPLC/MS in serum, we have newly designed a series of modified MHP1 peptides and have found that N-terminal acetylation and C-terminal amidation in MHP1 (MHP1-AcN), can strengthen its anti-inflammatory effects and increase its stability with anti-osteoclastogenic effects...
December 11, 2018: Scientific Reports
Hong-Yun He, Lu Ren, Tao Guo, Yi-Hao Deng
Ischemic stroke often induces excessive neuronal autophagy, resulting in brain damage; meanwhile, inflammatory responses stimulated by ischemia exacerbate neural injury. However, interactions between neuronal autophagy and microglial inflammation following ischemic stroke are poorly understood. CX3CL1/fractalkine, a membrane-bound chemokine expressed on neurons, can suppress microglial inflammation by binding to its receptor CX3CR1 on microglia. In the present study, to investigate whether autophagy could alter CX3CL1 expression on neurons and consequently change microglial inflammatory activity, middle cerebral artery occlusion (MCAO) was established in Sprague-Dawley rats to model ischemic stroke, and tissues from the ischemic penumbra were obtained to evaluate autophagy level and microglial inflammatory activity...
February 2019: Neural Regeneration Research
Elmina Mammadova-Bach, Magdolna Nagy, Johan W M Heemskerk, Bernhard Nieswandt, Attila Braun
Cytosolic free calcium (Ca2+ ) is a second messenger regulating a wide variety of functions in blood cells, including adhesion, activation, proliferation and migration. Store-operated Ca2+ entry (SOCE), triggered by depletion of Ca2+ from the endoplasmic reticulum, provides a main mechanism of regulated Ca2+ influx in blood cells. SOCE is mediated and regulated by isoforms of the ion channel proteins ORAI and TRP, and the transmembrane Ca2+ sensors stromal interaction molecules (STIMs), respectively. This report provides an overview of the (patho)physiological importance of SOCE in blood cells implicated in thrombosis and thrombo-inflammation, i...
November 23, 2018: Cell Calcium
Kecheng Zhou, Jiayu Wu, Jie Chen, Ye Zhou, Xiaolong Chen, Qiaoyun Wu, Yangxinzi Xu, Wenzhan Tu, Xinfa Lou, Guanhu Yang, Songhe Jiang
BACKGROUND: Neuroinflammation plays a major role in the development of ischemic stroke, and regulation of the proinflammatory TLR4 signaling pathway in microglia stands to be a promising therapeutic strategy for stroke intervention. Recently, the homeostasis of mitochondrial dynamics has also been raised as a vital component in maintaining neuronal health, but its relevance in microglia hasn't been investigated. Schaftoside, a natural flavonoid compound and a promising treatment for inflammation, has demonstrated potency against LPS-induced lung inflammation in mice; however, its action on TLR4-induced neuroinflammation and mitochondrial dynamics in microglia is still unknown...
November 25, 2018: Journal of Pharmacological Sciences
Gila Pirzad Jahromi, Alireza P Shabanzadeh, Mina Mokhtari Hashtjini, Seyed Shahabeddin Sadr, Javad Rasouli Vani, Javad Raouf Sarshoori, Jason Charish
Objectives: The beneficial outcomes of bone marrow-derived mesenchymal stem cell (BMSC) treatment on functional recovery following stroke has been well established. Furthermore, 5-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors have also been shown to increase neuronal survival and promote the movement of BMSCs towards the sites of inflammation. However, the precise mechanisms mediating the improved neurological functional recovery in stoke models following a combination treatment of Simvastatin and BMSCs still remained poorly understood...
October 2018: Iranian Journal of Basic Medical Sciences
Ignacio M Seropian, Germán E González, Sebastián M Maller, Daniel H Berrocal, Antonio Abbate, Gabriel A Rabinovich
Galectin-1 (Gal-1), an evolutionarily conserved β -galactoside-binding lectin, controls immune cell homeostasis and tempers acute and chronic inflammation by blunting proinflammatory cytokine synthesis, engaging T-cell apoptotic programs, promoting expansion of T regulatory (Treg) cells, and deactivating antigen-presenting cells. In addition, this lectin promotes angiogenesis by co-opting the vascular endothelial growth factor receptor (VEGFR) 2 signaling pathway. Since a coordinated network of immunomodulatory and proangiogenic mediators controls cardiac homeostasis, this lectin has been proposed to play a key hierarchical role in cardiac pathophysiology via glycan-dependent regulation of inflammatory responses...
2018: Mediators of Inflammation
V Yu Titov, A V Ivanova, V A Petrov, A N Osipov, S V Chausova, P R Kamchatnov
AIM: To study diagnostic possibilities for determining the content of nitrite and N-nitroso compounds (NO2 - +RNNO) in blood plasma and cerebrospinal fluid (CSF) in patients with acute ischemic stroke (IS). MATERIAL AND METHODS: Twenty-four patients with IS were examined. The content of NO oxidation products was determined in venous blood and CSF by using an enzyme sensor based on the unique property of nitrite (NO2 - ), N-nitroso compounds (RNNO), S-nitrosothiols and dinitrosyl iron complexes to inhibit the enzyme catalase in the presence of halide ions...
2018: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Ana Rita Castro, Sara Oliveira Silva, Sandra Clara Soares
Cardiovascular diseases (CVDs) are responsible for a high mortality rate worldwide. One of the most common causes of CVDs is vascular inflammation associated to atherosclerosis. Inflammatory biomarkers are used to assist the detection of CVDs and monitor their evaluation, prognosis and therapy implementation. C-reactive protein (CRP) is an acute phase protein produced after stimulation by pro-inflammatory cytokines. CRP is a biomarker of the inflammatory reaction and an important mediator of atherosclerosis...
2018: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
Xingyu Chen, Xiaorong Zhuang, Zhongwei Peng, Huili Yang, Liangyi Chen, Qingwei Yang
BACKGROUND: To assess whether intensive statin therapy reduces the occurrence of microemboli in patients with acute ischemic stroke. METHODS: Patients with acute ischemic stroke within 72 h of onset were randomized to the intensive statin (atorvastatin 60 mg/day, adjusted to 20 mg/day after 7 days) and control (atorvastatin 20 mg/day) groups. Combined aspirin and clopidogrel were used for antiplatelet therapy. Microemboli were monitored by transcranial Doppler on days 1 (pre-treatment), 3, and 7...
November 28, 2018: European Neurology
Wenson D Rajan, Bartosz Wojtas, Bartlomiej Gielniewski, Anna Gieryng, Malgorzata Zawadzka, Bozena Kaminska
Ischemic brain injury causes local inflammation, which involves activation of resident microglia, leukocyte, and monocyte infiltration. Involvement of peripheral immune cells in ischemia-induced damage and repair is debatable. Using flow cytometry, gene expression profiling, and immunocytochemistry, we show that microglia predominate in the ischemic brain and express inflammation mediators at Day 1 after transient middle cerebral artery occlusion (MCAo) in rats. At Day 3, both resident microglia and bone marrow (BM)-derived macrophages are detected in the ischemic hemispheres and display unique transcriptomic profiles...
November 28, 2018: Glia
Kate Lykke Lambertsen, Bente Finsen, Bettina Hjelm Clausen
Inflammation is currently considered a prime target for the development of new stroke therapies. In the acute phase of ischemic stroke, microglia are activated and then circulating immune cells invade the peri-infarct and infarct core. Resident and infiltrating cells together orchestrate the post-stroke inflammatory response, communicating with each other and the ischemic neurons, through soluble and membrane-bound signaling molecules, including cytokines. Inflammation can be both detrimental and beneficial at particular stages after a stroke...
November 27, 2018: Acta Neuropathologica
Jens T Rosenberg, Xuegang Yuan, Shannon N Helsper, F Andrew Bagdasarian, Teng Ma, Samuel C Grant
Ischemia, which involves decreased blood flow to a region and a corresponding deprivation of oxygen and nutrients, can be induced as a consequence of stroke or heart attack. A prevalent disease that affects many individuals worldwide, ischemic stroke results in functional and cognitive impairments, as neural cells in the brain receive inadequate nourishment and encounter inflammation and various other detrimental toxic factors that lead to their death. Given the scarce treatments for this disease in the clinic such as the administration of tissue plasminogen activator, which is only effective in a limited time window after the occurrence of stroke, it will be necessary to develop new strategies to ameliorate or prevent stroke-induced brain damage...
July 2018: Brain Circulation
Gabrielle Mangin, Nathalie Kubis
Stroke is a major public health issue with limited treatment. The pharmacologically or mechanically removing of the clot is accessible to less than 10% of the patients. Stem cell therapy is a promising alternative strategy since it increases the therapeutic time window but many issues remain unsolved. To avoid a new dramatic failure when translating experimental data on the bedside, this review aims to highlight the indispensable checkpoints to make a successful clinical trial based on the current preclinical literature...
November 15, 2018: Stem Cell Reviews
Suowen Xu, Danielle Kamato, Peter J Little, Shinichi Nakagawa, Jaroslav Pelisek, Zheng Gen Jin
Atherosclerosis, the principal cause of cardiovascular death worldwide, is a pathological disease characterized by fibro-proliferation, chronic inflammation, lipid accumulation, and immune disorder in the vessel wall. As the atheromatous plaques develop into advanced stage, the vulnerable plaques are prone to rupture, which causes acute cardiovascular events, including ischemic stroke and myocardial infarction. Emerging evidence has suggested that atherosclerosis is also an epigenetic disease with the interplay of multiple epigenetic mechanisms...
November 12, 2018: Pharmacology & Therapeutics
Hai-Rong Yu, Yue-Yue Wei, Jian-Guo Ma, Xiao-Yong Geng
OBJECTIVE: Both Aspirin and Clopidogrel are considered as effective drugs in decreasing ischemic events, which potentially contribute to a promising application regarding the cardiovascular events. In the present study, we evaluated the efficacy of the combination of both Clopidogrel and Aspirin to determine the influence among inflammatory factors, cardiac function, and treatment outcome of patients suffering from ST-segment elevation myocardial infarction (STEMI) in the Hebei province of China...
November 2018: Medicine (Baltimore)
Emily R Rosario, Stephanie E Kaplan, Sepehr Khonsari, Garrett Vazquez, Niyant Solanki, Melanie Lane, Hiriam Brownell, Sheila S Rosenberg
Background: While research suggests a benefit of hyperbaric oxygen therapy (HBOT) for neurologic injury, controlled clinical trials have not been able to clearly define the benefits. Objective: To investigate the effects of HBOT on physical and cognitive impairments resulting from an ischemic stroke. Methods: Using a within-subject design a baseline for current functional abilities was established over a 3-month period for all subjects (n=7)...
2018: Neurology Research International
Kar Wey Yong, Jane Ru Choi, Mehdi Mohammadi, Alim P Mitha, Amir Sanati-Nezhad, Arindom Sen
Ischemic diseases such as myocardial infarction, ischemic stroke, and critical limb ischemia are immense public health challenges. Current pharmacotherapy and surgical approaches are insufficient to completely heal ischemic diseases and are associated with a considerable risk of adverse effects. Alternatively, human mesenchymal stem cells (hMSCs) have been shown to exhibit immunomodulation, angiogenesis, and paracrine secretion of bioactive factors that can attenuate inflammation and promote tissue regeneration, making them a promising cell source for ischemic disease therapy...
2018: Stem Cells International
Chen Chen, Qi-Di Ai, Shi-Feng Chu, Zhao Zhang, Nai-Hong Chen
As a vital cell type in immune system and infiltrating cells in ischemic brain, NK cells can bridge the crosstalk between immune system and nervous system in stroke setting. The mechanism of action of NK cells is complicated, involving direct and indirect actions. NK cells are closely associated with poststroke inflammation, immunodepression and infections. The excessive inflammatory response in ischemic brain is one of the important causes for aggravating cerebral ischemic injury. Besides the inflammation induced by ischemia itself, thrombolytic drug tissue plasminogen activator (tPA) administration could also induce deteriorative inflammation, which is unfavorable for stroke control and recovery...
November 3, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Maarten J G Leening, Nancy R Cook, Oscar H Franco, JoAnn E Manson, Kamakshi Lakshminarayan, Michael J LaMonte, Enrique C Leira, Jennifer G Robinson, Paul M Ridker, Nina P Paynter
Background Cardiovascular risk factors have differential effects on various manifestations of cardiovascular disease, but to date direct formal comparisons are scarce, have been conducted primarily in men, and include only traditional risk factors. Methods and Results Using data from the multi-ethnic Women's Health Initiative Observational Study, we used a case-cohort design to compare 1731 women with incident cardiovascular disease during follow-up to a cohort of 1914 women. The direction of effect of all 24 risk factors (including various apolipoproteins, hemoglobin A1c , high-sensitivity C-reactive protein, N-terminal pro-brain natriuretic peptide, and tissue plasminogen activator antigen) was concordant for coronary heart disease (CHD, defined as myocardial infarction and CHD death) and ischemic stroke; however, associations were generally stronger with CHD...
October 2, 2018: Journal of the American Heart Association
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