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Macrophage stroke

Mei Jiang, Xinghui Liu, Denghai Zhang, Ying Wang, Xiaoxia Hu, Fengxia Xu, Mingming Jin, Fanfan Cao, Limin Xu
BACKGROUND: Acute ischemic stroke (AIS) is the most common type of cerebrovascular disease and is a leading cause of disability and death worldwide. Recently, a study suggested that transformation of microglia from the pro-inflammatory M1 state to the anti-inflammatory and tissue-reparative M2 phenotype may be an effective therapeutic strategy for ischemic stroke. Celastrol, a traditional oriental medicine, may have anti-inflammatory and neuroprotective effects. However, the underlying mechanisms remain unknown...
March 14, 2018: Journal of Neuroinflammation
Magda R Hamczyk, Ricardo Villa-Bellosta, Pilar Gonzalo, María J Andrés-Manzano, Paula Nogales, Jacob F Bentzon, Carlos López-Otín, Vicente Andrés
Background -Progerin, an aberrant protein that accumulates with age, causes the rare genetic disease Hutchinson-Gilford progeria syndrome (HGPS). HGPS patients with ubiquitous progerin expression exhibit accelerated aging and atherosclerosis, and die in their early teens mainly from myocardial infarction or stroke. The mechanisms underlying progerin-induced atherosclerosis remain unexplored, in part due to the lack of appropriate animal models. Methods -We generated an atherosclerosis-prone model of HGPS by crossing apolipoprotein E-deficient ( Apoe-/- ) mice with LmnaG609G/G609G mice ubiquitously expressing progerin...
February 28, 2018: Circulation
Yi-Je Chen, Hai M Nguyen, Izumi Maezawa, Lee-Way Jin, Heike Wulff
Objective: Inhibitors of the voltage-gated K+ channel Kv1.3 are currently in development as immunomodulators for the treatment of autoimmune diseases. As Kv1.3 is also expressed on microglia and has been shown to be specifically up-regulated on "M1-like" microglia, we here tested the therapeutic hypothesis that the brain-penetrant small-molecule Kv1.3-inhibitor PAP-1 reduces secondary inflammatory damage after ischemia/reperfusion. Methods: We studied microglial Kv1...
February 2018: Annals of Clinical and Translational Neurology
Wei Zhu, Yufeng Gao, Jieru Wan, Xi Lan, Xiaoning Han, Shanshan Zhu, Weidong Zang, Xuemei Chen, Wendy Ziai, Daniel F Hanley, Scott J Russo, Ricardo E Jorge, Jian Wang
Intracerebral hemorrhage (ICH) is a detrimental type of stroke. Mouse models of ICH, induced by collagenase or blood infusion, commonly target striatum, but not other brain sites such as ventricular system, cortex, and hippocampus. Few studies have systemically investigated brain damage and neurobehavioral deficits that develop in animal models of ICH in these areas of the right hemisphere. Therefore, we evaluated the brain damage and neurobehavioral dysfunction associated with right hemispheric ICH in ventricle, cortex, hippocampus, and striatum...
February 16, 2018: Brain, Behavior, and Immunity
Ryoko Umebayashi, Haruhito A Uchida, Yuki Kakio, Venkateswaran Subramanian, Alan Daugherty, Jun Wada
OBJECTIVE: Abdominal aortic aneurysm (AAA) is a permanent dilation of the abdominal aorta associated with rupture, which frequently results in fatal consequences. AAA tissue is commonly characterized by localized structural deterioration accompanied with inflammation and profound accumulation of leukocytes, although the specific function of these cells is unknown. Cilostazol, a phosphodiesterase III inhibitor, is commonly used for patients with peripheral vascular disease or stroke because of its anti-inflammatory effect, which is vasoprotective effects through its anti-inflammatory effect...
February 8, 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
Dan-Dan Dang, Hexige Saiyin, Qiong Yu, Wei-Min Liang
AIM: The effects of sevoflurane on microglia/macrophages, promoting or suppressing their activation, remains controversy. We aimed to determine whether sevoflurane preconditioning can protect brain via changing microglia/macrophage dynamics and phagocytosis profile after ischemia. METHODS: The impact of sevoflurane preconditioning was evaluated on microglia/macrophage migration, phagocytosis and proliferation altogether from day 1 to day 7 after transient middle cerebral arterial occlusion (tMCAO) in rats...
February 9, 2018: CNS Neuroscience & Therapeutics
Xiangrong Liu, Shaohong Wen, Feng Yan, Kuan Liu, Liqiang Liu, Lei Wang, Shangfeng Zhao, Xunming Ji
BACKGROUND: Following stroke, microglia can be driven to the "classically activated" pro-inflammatory (M1) phenotype and the "alternatively activated" anti-inflammatory (M2) phenotype. Salidroside (SLDS) is known to inhibit inflammation and to possess protective effects in neurological diseases, but to date, the exact mechanisms involved in these processes after stroke have yet to be elucidated. The purpose of this study was to determine the effects of SLDS on neuroprotection and microglial polarization after stroke...
February 9, 2018: Journal of Neuroinflammation
Ankita Solanki, Lokesh Kumar Bhatt, Thomas P Johnston
Atherosclerosis is a progressive disease of large arteries and a leading cause of cardiovascular diseases and stroke. Chronic inflammation, aberrant immune response, and disturbances to key enzymes involved with lipid metabolism are characteristic features of atherosclerosis. Apart from targeting the derangements in lipid metabolism, therapeutic modulation to regulate chronic inflammation and the immune system response may prove to be very promising strategies in the management of atherosclerosis. In recent years, various targets have been studied for the treatment of atherosclerosis...
February 4, 2018: Pharmacology & Therapeutics
Bin Xiang, Chun Xiao, Ting Shen, Xiufang Li
Inflammation plays a pivotal role in the pathogenesis of ischemic stroke. The inhibition of inflammation appears to be a potential therapeutic strategy for neuro-inflammatory injury after ischemic stroke. In response to cerebral ischemia, resident microglia and infiltrated macrophages from the damaged blood-brain barrier are activated. Microglia activation appears to be a double-edged sword. Activated microglia migrate to the damaged neuron, change their phenotype to M1 or M2, and become involved in nerve damage and repair...
January 29, 2018: Molecular Immunology
Jin A Shin, Yul A Kim, Hye Won Kim, Hee-Sun Kim, Kyung-Eun Lee, Jihee Lee Kang, Eun-Mi Park
We previously reported that the bone morphogenetic protein (BMP) antagonist, noggin, improved the repair process with an increase in the reactive microglia/macrophage population in the ischemic brain. Since BMP plays a role in intracellular iron homeostasis via the hepcidin/ferroportin axis, and iron is required for myelination, this study was aimed to determine whether noggin affected iron status and remyelination in the brain following ischemic stroke. We further examined the effect of blocking the BMP/hepcidin pathway on reactive microglia (BV2) and myelination of oligodendroglial cells (MO3...
January 30, 2018: Neuropharmacology
H M H Spronk, T Padro, J E Siland, J H Prochaska, J Winters, A C van der Wal, J J Posthuma, G Lowe, E d'Alessandro, P Wenzel, D M Coenen, P H Reitsma, W Ruf, R H van Gorp, R R Koenen, T Vajen, N A Alshaikh, A S Wolberg, F L Macrae, N Asquith, J Heemskerk, A Heinzmann, M Moorlag, N Mackman, P van der Meijden, J C M Meijers, M Heestermans, T Renné, S Dólleman, W Chayouâ, R A S Ariëns, C C Baaten, M Nagy, A Kuliopulos, J J Posma, P Harrison, M J Vries, H J G M Crijns, E A M P Dudink, H R Buller, Y M C Henskens, A Själander, S Zwaveling, O Erküner, J W Eikelboom, A Gulpen, F E C M Peeters, J Douxfils, R H Olie, T Baglin, A Leader, U Schotten, B Scaf, H M M van Beusekom, L O Mosnier, L van der Vorm, P Declerck, M Visser, D W J Dippel, V J Strijbis, K Pertiwi, A J Ten Cate-Hoek, H Ten Cate
Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics: 1...
February 2018: Thrombosis and Haemostasis
Andrew N Clarkson, Lily Boothman-Burrell, Zita Dósa, Raghavendra Y Nagaraja, Liang Jin, Kim Parker, Petra S van Nieuwenhuijzen, Silke Neumann, Emma K Gowing, Navnath Gavande, Philip K Ahring, Mai M Holm, Jane R Hanrahan, Joseph A Nicolazzo, Kimmo Jensen, Mary Chebib
Tonic inhibitory currents, mediated by extrasynaptic GABAA receptors, are elevated at a delay following stroke. Flavonoids minimise the extent of cellular damage following stroke, but little is known about their mode of action. We demonstrate that the flavonoid, 2'-methoxy-6-methylflavone (0.1-10 µM; 2'MeO6MF), increases GABAA receptor tonic currents presumably via δ-containing GABAA receptors. Treatment with 2'MeO6MF 1-6 h post focal ischaemia dose dependently decreases infarct volume and improves functional recovery...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
Jan Boddaert, Kenny Bielen, Bart 's Jongers, Ekta Manocha, Laetitia Yperzeele, Patrick Cras, Daniel Pirici, Samir Kumar-Singh
Classical or M1 activity of microglia/macrophages has been described in several neurodegenerative and brain inflammatory conditions and has also been linked to expansion of ischemic injury in post-stroke brain. While different pathways of M1 polarization have been suggested to occur in the post-stroke brain, the precise underlying mechanisms remain undefined. Using a transient middle cerebral artery occlusion (MCAO) rat model, we showed a progressive M2 to M1 polarization in the perilesional brain region with M1 cells becoming one of the dominant subsets by day 4 post-stroke...
2018: PloS One
Willie Lin, Yogi Chang-Yo Hsuan, Mao-Tsun Lin, Ting-Wei Kuo, Cheng-Hsien Lin, Yu-Chin Su, Ko-Chi Niu, Ching-Ping Chang, Hung-Jung Lin
Microglia are the first source of a neuroinflammatory cascade, which seems to be involved in every phase of stroke-related neuronal damage. Two weeks after transient middle cerebral artery occlusion (MCAO), vehicle-treated rats displayed higher numbers of total ionized calcium-binding adaptor molecule 1 (Iba-1)-positive cells, greater cell body areas of Iba-1-positive cells, and higher numbers of hypertrophic Iba-1-positive cells (with a cell body area over 80 μm2) in the ipsilateral ischemic brain regions including the frontal cortex, striatum, and parietal cortex...
November 2017: Cell Transplantation
Eri Iwasawa, Satoru Ishibashi, Motohiro Suzuki, FuYing Li, Masahiko Ichijo, Kazunori Miki, Takanori Yokota
BACKGROUND: Development of collateral circulation after acute ischemic stroke is triggered by shear stress that occurs in pre-existing arterioles. Recently, sphingosine-1-phosphate receptor 1 (S1P1) on endothelial cells was reported to sense shear stress and transduce its signaling pathways. METHODS: BALB/c mice (n = 118) were subjected to permanent middle cerebral artery occlusion (pMCAO) or sham operation. We investigated the effect of an S1P1-selective agonist SEW2871 on leptomeningeal collateral arteries and neurological outcome after pMCAO...
January 11, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Ze-Mou Yu, Xiao-Tao Deng, Ruo-Mei Qi, Lu-Yan Xiao, Chong-Qing Yang, Tao Gong
BACKGROUND: Chronic stress contributes to increased risks of atherosclerotic diseases including heart disease, stroke, and transient ischemic attack. However, its underline mechanisms are poorly understood. This study aimed to elucidate the mechanism via which chronic stress exerts its effect on atherosclerosis (AS). METHODS: Fifty male New Zealand white rabbits were used. Aortic balloon-injury model was applied. Both social stress and physical stress methods were adopted to establish chronic stress models...
January 20, 2018: Chinese Medical Journal
Georgios Tsivgoulis, Aristeidis H Katsanos, Georgios Giannopoulos, Vasiliki Panagopoulou, Dalius Jatuzis, Robin Lemnens, Spyridon Deftereos, Peter J Kelly
INTRODUCTION: Despite the proven efficacy of anti-thrombotic, lipid-lowering, anti-hypertensive therapies and lifestyle modification changes for secondary ischemic stroke prevention, the risk of recurrent stroke, coronary events and vascular death remains substantial even for patients treated with high rates of established secondary preventive medications. METHODS: In the present review, we summarize available literature data on the association between systemic inflammation and symptomatic atherosclerosis including recurrent cerebral ischemia...
January 15, 2018: Current Pharmaceutical Design
Tonje Skarpengland, Mona Skjelland, Xiang Yi Kong, Karolina Skagen, Sverre Holm, Kari Otterdal, Christen P Dahl, Kirsten Krohg-Sørensen, Ellen L Sagen, Vigdis Bjerkeli, Anne Hege Aamodt, Azhar Abbas, Ida Gregersen, Pål Aukrust, Bente Halvorsen, Tuva B Dahl
BACKGROUND: Soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) has been shown to be increased in patients with acute ischemic stroke. Here, we evaluated plasma sLOX-1 levels and vascular carotid plaque LOX-1 (ie, OLR1) gene expression in patients with ischemic stroke and transient ischemic attack (TIA) with particular focus on their relation to time since symptom onset. METHODS AND RESULTS: Plasma sLOX-1 (n=232) and carotid plaque OLR1 gene expression (n=146) were evaluated in patients who were referred to evaluation for carotid endarterectomy, as well as in healthy control plasma (n=81)...
January 12, 2018: Journal of the American Heart Association
Federico Carbone, Fabio Rigamonti, Fabienne Burger, Aline Roth, Maria Bertolotto, Giovanni Spinella, Bianca Pane, Domenico Palombo, Aldo Pende, Aldo Bonaventura, Luca Liberale, Alessandra Vecchié, Franco Dallegri, François Mach, Fabrizio Montecucco
BACKGROUND: Inflammatory mediators in the blood stream and within plaques are key determinants in atherogenesis. Here, we investigated serum osteopontin (OPN) as a potential predictor of poor outcome in patients with severe carotid atherosclerosis. METHODS: Carotid plaques and serum were collected from patients asymptomatic (n=185) or symptomatic (n=40) for ischemic stroke. Plaques were stained for lipids, smooth muscle cells, neutrophils, M1 and M2 macrophage subsets and matrix metallopropteinase-9 (MMP-9)...
January 5, 2018: International Journal of Cardiology
Cora H Nijboer, Elke Kooijman, Cindy T van Velthoven, Erik van Tilborg, Ivo A Tiebosch, Niels Eijkelkamp, Rick M Dijkhuizen, Jozef Kesecioglu, Cobi J Heijnen
Subarachnoid hemorrhage (SAH) represents a major health problem in Western society due to high mortality and morbidity, and the relative young age of patients. Currently, efficacious therapeutic options are very limited. Mesenchymal stem cell (MSC) administration has been shown to improve functional outcome and lesion size in experimental models of stroke and neonatal hypoxic-ischemic brain injury. Here, we studied the therapeutic potential of intranasally administered bone marrow-derived MSCs relatively late postinsult using a rat endovascular puncture model for SAH...
March 1, 2018: Stem Cells and Development
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