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https://www.readbyqxmd.com/read/29769800/the-therapeutic-potential-of-blocking-galectin-3-expression-in-acute-myocardial-infarction-and-mitigating-inflammation-of-infarct-region-a-clinical-outcome-based-translational-study
#1
Wassim Mosleh, Milind R Chaudhari, Swati Sonkawade, Supriya Mahajan, Charl Khalil, Kevin Frodey, Tanvi Shah, Suraj Dahal, Roshan Karki, Rujuta Katkar, W Matthijs Blankesteijn, Brian Page, Saraswati Pokharel, Minhyung Kim, Umesh C Sharma
Introduction: Increased galectin-3 is associated with ischemic cardiomyopathy, although its role in early remodeling post-myocardial infarction (MI) has not been fully elucidated. There are no data demonstrating that blocking galectin-3 expression would have an impact on the heart and that its relationship to remodeling is not simply an epiphenomenon. The direct association between galectin-3 and myocardial inflammation, dysfunction, and adverse cardiovascular outcomes post-MI was examined using clinical and translational studies...
2018: Biomarker Insights
https://www.readbyqxmd.com/read/29766045/post-stroke-intranasal-naloxone-delivery-reduces-microglial-activation-and-improves-behavioral-recovery-from-ischemic-injury
#2
Jenni E Anttila, Katrina Albert, Emily S Wires, Kert Mätlik, Lisa C Loram, Linda R Watkins, Kenner C Rice, Yun Wang, Brandon K Harvey, Mikko Airavaara
Ischemic stroke is the leading cause of disability, and effective therapeutic strategies are needed to promote complete recovery. Neuroinflammation plays a significant role in stroke pathophysiology, and there is limited understanding of how it affects recovery. The aim of this study was to characterize the spatiotemporal expression profile of microglial activation and whether dampening microglial/macrophage activation post-stroke facilitates the recovery. For dampening microglial/macrophage activation, we chose intranasal administration of naloxone, a drug that is already in clinical use for opioid overdose and is known to decrease microglia/macrophage activation...
March 2018: ENeuro
https://www.readbyqxmd.com/read/29759141/elevated-plasma-macrophage-migration-inhibitor-factor-as-a-risk-factor-for-the-development-of-post-stroke-depression-in-ischemic-stroke
#3
Tingting Xu, Shuang Pu, Ying Ni, Mingqing Gao, Xuemei Li, Xianwei Zeng
BACKGROUND: Macrophage migration inhibitory factor (MIF), a central cytokine of the innate immunity and inflammatory responses, has been reported to link to the pathophysiology of cardiovascular disease and depression. The aim of this study was to test the possible association between plasma MIF and the development of post-stroke depression (PSD) in Chinese patients with acute ischemic stroke (AIS). METHODS: The first-ever AIS patients who were hospitalized at Affiliated Hospital of Weifang Medical College during the period from November 2015 to September 2017 were included...
July 15, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29750575/unified-nexus-of-macrophages-and-maresins-in-cardiac-reparative-mechanisms
#4
Jeevan Kumar Jadapalli, Ganesh V Halade
Macrophages are immune-sensing "big eater" phagocytic cells responsible for an innate, adaptive, and regenerative response. After myocardial infarction, macrophages predominantly clear the deceased cardiomyocyte apoptotic or necrotic neutrophils to develop a regenerative and reparative program with the activation of the lipoxygenase-mediated maresin (MaR) metabolome at the site of ischemic injury. The specialized proresolving molecule and macrophage mediator in resolving inflammation, MaR-1, produced by human macrophages, has potent defining effects that limit polymorphonuclear neutrophil infiltration, enhance uptake of apoptotic PMNs, regulate inflammation resolution and tissue regeneration, and reduce pain...
May 11, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29743976/cell-type-specific-mechanisms-in-the-pathogenesis-of-ischemic-stroke-the-role-of-apoptosis-signal-regulating-kinase-1
#5
REVIEW
So Yeong Cheon, Eun Jung Kim, Jeong Min Kim, Bon-Nyeo Koo
Stroke has become a more common disease worldwide. Despite great efforts to develop treatment, little is known about ischemic stroke. Cerebral ischemia activates multiple cascades of cell type-specific pathomechanisms. Ischemic brain injury consists of a complex series of cellular reactions in various cell types within the central nervous system (CNS) including platelets, endothelial cells, astrocytes, neutrophils, microglia/macrophages, and neurons. Diverse cellular changes after ischemic injury are likely to induce cell death and tissue damage in the brain...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29736174/diabetic-ephrin-b2-stimulated-peripheral-blood-mononuclear-cells-enhance-poststroke-recovery-in-mice
#6
Rose Hilal, Marine Poittevin, Adrien Pasteur-Rousseau, Adrien Cogo, Gabrielle Mangin, Marie Chevauché, Yasmine Ziat, José Vilar, Jean-Marie Launay, Jean-François Gautier, Dong Broquères-You, Bernard I Levy, Tatyana Merkulova-Rainon, Nathalie Kubis
Clinical trials of cell therapy in stroke favor autologous cell transplantation. To date, feasibility studies have used bone marrow-derived mononuclear cells, but harvesting bone marrow cells is invasive thus complicating bedside treatment. We investigated the therapeutic potential of peripheral blood-derived mononuclear cells (PB-MNC) harvested from diabetic patients and stimulated by ephrin-B2 (PB-MNC+) (500,000 cells), injected intravenously 18-24 hours after induced cerebral ischemia in mice. Infarct volume, neurological deficit, neurogenesis, angiogenesis, and inflammation were investigated as were the potential mechanisms of PB-MNC+ cells in poststroke neurorepair...
2018: Stem Cells International
https://www.readbyqxmd.com/read/29719282/intravenously-delivered-allogeneic-mesenchymal-stem-cells-bidirectionally-regulate-inflammation-and-induce-neurotrophic-effects-in-distal-middle-cerebral-artery-occlusion-rats-within-the-first-7-days-after-stroke
#7
XiaoBo Li, Min Huang, RenChao Zhao, ChunSong Zhao, Yao Liu, HaiQiang Zou, Ling Chen, YunQian Guan, Y Alex Zhang
BACKGROUND/AIMS: Neurotrophic effects and immunosuppression are the main therapeutic mechanisms of mesenchymal stem cells (MSCs) in stroke treatment. Neurotrophins are produced by graft cells, host neurons, astrocytes, and even microglia/macrophages. Meanwhile, MSCs can increase inflammation if they are not sufficiently induced by pro-inflammatory cytokines. We examined whether intravenously transplanted bone marrow MSCs (BM-MSCs) increase inflammation in distal middle cerebral artery occlusion (dMCAO) rats, how long the increased inflammation effect persists for, and what the final therapeutic outcomes will be...
April 26, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29651892/the-intracerebral-hemorrhage-blood-transcriptome-in-humans-differs-from-the-ischemic-stroke-and-vascular-risk-factor-control-blood-transcriptomes
#8
Boryana Stamova, Bradley P Ander, Glen Jickling, Farah Hamade, Marc Durocher, Xinhua Zhan, Da Zhi Liu, Xiyuan Cheng, Heather Hull, Alan Yee, Kwan Ng, Natasha Shroff, Frank R Sharp
Understanding how the blood transcriptome of human intracerebral hemorrhage (ICH) differs from ischemic stroke (IS) and matched controls (CTRL) will improve understanding of immune and coagulation pathways in both disorders. This study examined RNA from 99 human whole-blood samples using GeneChip® HTA 2.0 arrays to assess differentially expressed transcripts of alternatively spliced genes between ICH, IS and CTRL. We used a mixed regression model with FDR-corrected p(Dx) < 0.2 and p < 0.005 and |FC| > 1...
January 1, 2018: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/29650950/interleukin-1-receptor-antagonist-mediated-neuroprotection-by-umbilical-cord-derived-mesenchymal-stromal-cells-following-transplantation-into-a-rodent-stroke-model
#9
Seung-Hun Oh, Chunggab Choi, Jeong-Eun Noh, Nayeon Lee, Yong-Woo Jeong, Iksoo Jeon, Jeong-Min Shin, Ji-Hye Kim, Ho-Jin Kim, Ji-Min Lee, Hyun-Sook Kim, Ok-Joon Kim, Jihwan Song
The human umbilical cord is a promising source of mesenchymal stromal cells (MSCs). Intravenous administration of human umbilical cord-derived MSCs (IV-hUMSCs) showed a favorable effect in a rodent stroke model by a paracrine mechanism. However, its underlying therapeutic mechanisms must be determined for clinical application. We investigated the therapeutic effects and mechanisms of our good manufacturing practice (GMP)-manufactured hUMSCs using various cell doses and delivery time points in a rodent model of stroke...
April 13, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29643512/innate-immune-memory-in-the-brain-shapes-neurological-disease-hallmarks
#10
Ann-Christin Wendeln, Karoline Degenhardt, Lalit Kaurani, Michael Gertig, Thomas Ulas, Gaurav Jain, Jessica Wagner, Lisa M Häsler, Katleen Wild, Angelos Skodras, Thomas Blank, Ori Staszewski, Moumita Datta, Tonatiuh Pena Centeno, Vincenzo Capece, Md Rezaul Islam, Cemil Kerimoglu, Matthias Staufenbiel, Joachim L Schultze, Marc Beyer, Marco Prinz, Mathias Jucker, André Fischer, Jonas J Neher
Innate immune memory is a vital mechanism of myeloid cell plasticity that occurs in response to environmental stimuli and alters subsequent immune responses. Two types of immunological imprinting can be distinguished-training and tolerance. These are epigenetically mediated and enhance or suppress subsequent inflammation, respectively. Whether immune memory occurs in tissue-resident macrophages in vivo and how it may affect pathology remains largely unknown. Here we demonstrate that peripherally applied inflammatory stimuli induce acute immune training and tolerance in the brain and lead to differential epigenetic reprogramming of brain-resident macrophages (microglia) that persists for at least six months...
April 11, 2018: Nature
https://www.readbyqxmd.com/read/29576323/immunomodulatory-treatment-with-systemic-gm-csf-augments-pulmonary-immune-responses-and-improves-neurological-outcome-after-experimental-stroke
#11
Claudia Dames, Katarzyna Winek, Yasmin Beckers, Odilo Engel, Andreas Meisel, Christian Meisel
Stroke-induced immunodepression is an independent risk factor for stroke-associated pneumonia (SAP). Granulocyte-macrophage colony stimulating factor (GM-CSF) has neuroprotective properties in experimental stroke and been demonstrated to reverse immunodepression in sepsis patients. However, whether GM-CSF restores immune function after stroke preventing SAP and improving outcome is unknown. Here, we demonstrated that GM-CSF treatment improved peripheral and pulmonary leukocyte numbers, peripheral cytokine responses, lowered lung bacterial burden in the early course and improved long-term functional outcome after experimental stroke...
March 9, 2018: Journal of Neuroimmunology
https://www.readbyqxmd.com/read/29568329/differential-immunological-profiles-herald-magnetic-resonance-imaging-defined-perioperative-cerebral-infarction
#12
Jonathon P Fanning, Louise E See Hoe, Margaret R Passmore, Adrian G Barnett, Barbara E Rolfe, Jonathan E Millar, Allan J Wesley, Jacky Suen, John F Fraser
Background: The perioperative period is associated with a high risk for human ischaemic stroke. Although inflammatory mechanisms are known to have an important role in cerebral infarction in the nonoperative setting, their role in modulating perioperative risk remains unclear. Methods: In this prospective case-control study, we compared 10 patients (cases) who developed magnetic resonance imaging (MRI) evidence of cerebral infarction following transcatheter aortic valve implantation with 10 patients (controls) who underwent the same procedure without neurological complication...
2018: Therapeutic Advances in Neurological Disorders
https://www.readbyqxmd.com/read/29558307/cerebral-microbleeds-imaging-and-clinical-significance
#13
REVIEW
Sven Haller, Meike W Vernooij, Joost P A Kuijer, Elna-Marie Larsson, Hans Rolf Jäger, Frederik Barkhof
Cerebral microbleeds (CMBs), also referred to as microhemorrhages, appear on magnetic resonance (MR) images as hypointense foci notably at T2*-weighted or susceptibility-weighted (SW) imaging. CMBs are detected with increasing frequency because of the more widespread use of high magnetic field strength and of newer dedicated MR imaging techniques such as three-dimensional gradient-echo T2*-weighted and SW imaging. The imaging appearance of CMBs is mainly because of changes in local magnetic susceptibility and reflects the pathologic iron accumulation, most often in perivascular macrophages, because of vasculopathy...
April 2018: Radiology
https://www.readbyqxmd.com/read/29557374/dabrafenib-an-inhibitor-of-rip3-kinase-dependent-necroptosis-reduces-ischemic-brain-injury
#14
Shelly A Cruz, Zhaohong Qin, Alexandre F R Stewart, Hsiao-Huei Chen
Ischemic brain injury triggers neuronal cell death by apoptosis via caspase activation and by necroptosis through activation of the receptor-interacting protein kinases (RIPK) associated with the tumor necrosis factor-alpha (TNF-α)/death receptor. Recent evidence shows RIPK inhibitors are neuroprotective and alleviate ischemic brain injury in a number of animal models, however, most have not yet undergone clinical trials and safety in humans remains in question. Dabrafenib, originally identified as a B-raf inhibitor that is currently used to treat melanoma, was later revealed to be a potent RIPK3 inhibitor at micromolar concentrations...
February 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29548814/renin-and-aldosterone-are-not-associated-with-vulnerable-plaque-characteristics-in-patients-with-carotid-artery-disease
#15
Marieke A Hillaert, Hester M den Ruijter, Imo E Hoefer, Eef G Lentjes, Gert J de Borst, Jean-Paul P M de Vries, Pieter A Doevendans, Gerard Pasterkamp, Leo Timmers
BACKGROUND: The renin-angiotensin-aldosterone system is increasingly being recognized to play an important role in the development and clinical course of cardiovascular diseases. Renin-angiotensin-aldosterone system activation is associated with clinical outcome in various populations of cardiovascular patients, such as patients with coronary artery, peripheral artery, and cerebrovascular disease. In this study, we investigated the associations between plasma renin and aldosterone concentrations and atherosclerotic plaque characteristics and secondary vascular events in patients undergoing carotid endarterectomy...
March 13, 2018: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/29540209/celastrol-treatment-protects-against-acute-ischemic-stroke-induced-brain-injury-by-promoting-an-il-33-st2-axis-mediated-microglia-macrophage-m2-polarization
#16
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
https://www.readbyqxmd.com/read/29490993/vascular-smooth-muscle-specific-progerin-expression-accelerates-atherosclerosis-and-death-in-a-mouse-model-of-hutchinson-gilford-progeria-syndrome
#17
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
https://www.readbyqxmd.com/read/29468176/inhibition-of-the-potassium-channel-kv1-3-reduces-infarction-and-inflammation-in-ischemic-stroke
#18
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
https://www.readbyqxmd.com/read/29458197/changes-in-motor-function-cognition-and-emotion-related-behavior-after-right-hemispheric-intracerebral-hemorrhage-in-various-brain-regions-of-mouse
#19
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...
March 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29437572/cilostazol-attenuates-angiotensin-ii-induced-abdominal-aortic-aneurysms-but-not-atherosclerosis-in-apolipoprotein-e-deficient-mice
#20
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-platelet aggregation effect and anti-inflammatory effect, which is vasoprotective effect...
April 2018: Arteriosclerosis, Thrombosis, and Vascular Biology
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