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https://www.readbyqxmd.com/read/28736035/propane-2-sulfonic-acid-octadec-9-enyl-amide-a-novel-ppar%C3%AE-%C3%AE-dual-agonist-protects-against-ischemia-induced-brain-damage-in-mice-by-inhibiting-inflammatory-responses
#1
Ying Li, Lanxi Xu, Kaiyue Zeng, Zhentian Xu, Daqin Suo, Lu Peng, Tong Ren, Zhiheng Sun, Wushuang Yang, Xin Jin, Lichao Yang
Propane-2-sulfonic acid octadec-9-enyl-amide (N15), an analogue of oleoylethanolamide (OEA), is a novel PPARα/γ dual agonist. Our previous studies verified the positive effects of OEA on the acute and delayed stages of cerebral ischemia. However, it is not clear whether N15 is effective against ischemic cerebral injury. In the present study, male Kunming mice were subjected to middle cerebral artery occlusion (MCAO). To evaluate its preventive effects, N15 (50, 100 or 200 mg/kg, ip) was administered for 3 days before ischemia...
July 20, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28734077/integrative-studies-implicate-matrix-metalloproteinase-12-as-a-culprit-gene-for-large-artery-atherosclerotic-stroke
#2
Hovsep Mahdessian, Ljubica Perisic Matic, Mariette Lengquist, Karl Gertow, Bengt Sennblad, Damiano Baldassarre, Fabrizio Veglia, Steve E Humphries, Rainer Rauramaa, Ulf de Faire, Andries J Smit, Philippe Giral, Sudhir Kurl, Elmo Mannarino, Elena Tremoli, Anders Hamsten, Per Eriksson, Ulf Hedin, Anders Mälarstig
BACKGROUND: Ischemic stroke and coronary heart disease are important contributors to the global disease burden and share atherosclerosis as the main underlying cause. Recent evidence from a genome-wide association study (GWAS) suggested that single nucleotide polymorphisms (SNP) near the MMP12 gene at chromosome 11q22.3 were associated with large-vessel ischemic stroke. Here we evaluated and extended these results by examining the relationship between MMP12 and atherosclerosis in clinical and experimental studies...
July 22, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28732809/oleacein-may-inhibit-destabilization-of-carotid-plaques-from-hypertensive-patients-impact-on-high-mobility-group-protein-1
#3
Agnieszka Filipek, Monika E Czerwińska, Anna K Kiss, Jerzy A Polański, Marek Naruszewicz
BACKGROUND: In patients with hypertension the haemorrhage into carotid atherosclerotic plaque increases risk of plaque destabilization and rupture. Our previous study showed that oleacein, a secoiridoid present in extra virgin olive oil, enhanced uptake of haemoglobin-haptoglobin complex and change macrophage phenotype from pro-inflammatory M1 to anti-inflammatory M2. PURPOSE: The aim this study was to investigate a potential role of oleacein in attenuation of carotid plaque destabilisation ex vivo...
August 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28729134/macrophage-migration-inhibitory-factor-levels-in-serum-from-patients-with-acute-intracerebral-hemorrhage-potential-contribution-to-prognosis
#4
Qun Lin, Jian-Yong Cai, Chuan Lu, Jun Sun, Hua-Jun Ba, Mao-Hua Chen, Xian-Dong Chen, Jun-Xia Dai, Jian-Hu Lin
BACKGROUND: Intracerebral hemorrhage (ICH) pathophysiology involves inflammation. Macrophage migration inhibition factor (MIF), a pro-inflammatory cytokine, is related to prognosis of ischemic stroke. The aim of this study was to investigate whether serum MIF levels are associated with severity and outcomes in patients with acute ICH. METHODS: We enrolled a total of 120 consecutive ICH patients and 120 healthy controls and sampled blood on admission and at study entry respectively...
July 17, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28725968/microglial-mediated-pdgf-cc-activation-increases-cerebrovascular-permeability-during-ischemic-stroke
#5
Enming Joseph Su, Chunzhang Cao, Linda Fredriksson, Ingrid Nilsson, Christina Stefanitsch, Tamara K Stevenson, Juanjuan Zhao, Margret Ragsdale, Yu-Yo Sun, Manuel Yepes, Chia-Yi Kuan, Ulf Eriksson, Dudley K Strickland, Daniel A Lawrence, Li Zhang
Treatment of acute ischemic stroke with the thrombolytic tissue plasminogen activator (tPA) can significantly improve neurological outcomes; however, thrombolytic therapy is associated with an increased risk of intra-cerebral hemorrhage (ICH). Previously, we demonstrated that during stroke tPA acting on the parenchymal side of the neurovascular unit (NVU) can increase blood-brain barrier (BBB) permeability and ICH through activation of latent platelet-derived growth factor-CC (PDGF-CC) and signaling by the PDGF receptor-α (PDGFRα)...
July 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28713482/comparative-therapeutic-effects-of-minocycline-treatment-and-bone-marrow-mononuclear-cell-transplantation-following-striatal-stroke
#6
Celice C Souza, Michelle Castro da Silva, Rosana Telma Lopes, Marcelo M Cardoso, Lucas Lacerda de Souza, Adriano Guimarães Santos, Ijair Rogério Dos Santos, Edna C S Franco, Walace Gomes-Leal
We explored the comparative effects of minocycline treatment and intrastriatal BMMC transplantation after experimental striatal stroke in adult rats. Male Wistar adult rats were divided as follows: saline-treated (N = 5), minocycline-treated (N = 5), and BMMC-transplanted (N = 5) animals. Animals received intrastriatal microinjections of 80 pmol of endothelin-1 (ET-1). Behavioral tests were performed at 1, 3, and 7 days postischemia. Animals were treated with minocycline (50 mg/kg, i.p.) or intrastriatal transplants of 106 BMMCs at 24 h postischemia...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28691076/self-assembling-cyclic-d-l-%C3%AE-peptides-as-modulators-of-plasma-hdl-function-a-supramolecular-approach-toward-antiatherosclerotic-agents
#7
Yannan Zhao, Luke J Leman, Debra J Search, Ricardo A Garcia, David A Gordon, Bruce E Maryanoff, M Reza Ghadiri
There is great interest in developing new modes of therapy for atherosclerosis to treat coronary heart disease and stroke, particularly ones that involve modulation of high-density lipoproteins (HDLs). Here, we describe a new supramolecular chemotype for altering HDL morphology and function. Guided by rational design and SAR-driven peptide sequence enumerations, we have synthesized and determined the HDL remodeling activities of over 80 cyclic d,l-α-peptides. We have identified a few distinct sequence motifs that are effective in vitro in remodeling human and mouse plasma HDLs to increase the concentration of lipid-poor pre-beta HDLs, which are key initial acceptors of cholesterol in the reverse cholesterol transport (RCT) process, and concomitantly promote cholesterol efflux from macrophage cells...
June 28, 2017: ACS Central Science
https://www.readbyqxmd.com/read/28684538/tissue-type-plasminogen-activator-regulates-macrophage-activation-and-innate-immunity
#8
Elisabetta Mantuano, Pardis Azmoon, Coralie Brifault, Michael A Banki, Andrew S Gilder, Wendy M Campana, Steven L Gonias
Tissue-type plasminogen activator (tPA) is the major intravascular activator of fibrinolysis and a ligand for receptors involved in cell-signaling. In cultured macrophages, tPA inhibits the response to lipopolysaccharide (LPS) by a pathway that apparently requires LDL Receptor-related Protein-1 (LRP1). Herein, we show that the mechanism by which tPA neutralizes LPS involves rapid reversal of IκBα phosphorylation. tPA independently induced transient IκBα phosphorylation and ERK1/2 activation in macrophages; however, these events that did not trigger inflammatory mediator expression...
July 6, 2017: Blood
https://www.readbyqxmd.com/read/28679106/macrophage-migration-inhibitory-factor-a-multifaceted-cytokine-implicated-in-multiple-neurological-diseases
#9
REVIEW
Marcel F Leyton-Jaimes, Joy Kahn, Adrian Israelson
Macrophage migration inhibitory factor (MIF) is a conserved cytokine found as a homotrimer protein. It is found in a wide spectrum of cell types in the body including neuronal and non-neuronal cells. MIF is implicated in several biological processes; chemo-attraction, cytokine activity, and receptor binding, among other functions. More recently, a chaperone-like activity has been added to its repertoire. In this review, we focus on the implication of MIF in the central nervous system and peripheries, its role in neurological disorders, and the mechanisms by which MIF is regulated...
July 2, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/28678763/neuroprotective-effect-of-a-novel-gastrodin-derivative-against-ischemic-brain-injury-involvement-of-peroxiredoxin-and-tlr4-signaling-inhibition
#10
Xiao-Na Mao, Hong-Jing Zhou, Xiao-Jia Yang, Li-Xue Zhao, Xi Kuang, Chu Chen, Dong-Ling Liu, Jun-Rong Du
The inhibition of extracellular inflammatory peroxiredoxin (Prx) signaling appears to be a potential therapeutic strategy for neuroinflammatory injury after acute ischemic stroke. Gastrodin (Gas) is a phenolic glycoside that is used for the treatment of cerebral ischemia, accompanied by regulation of the autoimmune inflammatory response. The present study investigated the neuroprotective effects of Gas and its derivative, Gas-D, with a focus on the potential mechanism associated with inflammatory Prx-Toll-like receptor 4 (TLR4) signaling...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28677732/jnk-signaling-is-required-for-the-mip%C3%A2-1%C3%AE-%C3%A2-associated-regulation-of-kupffer-cells-in-the-heat-stroke-response
#11
Xiao-Juan Chen, Zhong-Zhi Tang, Guo-Guo Zhu, Qing Cheng, Wen-Kai Zhang, Hui-Min Li, Wei Fu, Qi-Ping Lu
Severe heat stroke (HS) consists of extreme hyperthermia with thermoregulatory failure, leading to high morbidity and mortality. Liver injury is a complication of HS that is associated with inflammatory responses and Kupffer cells (KCs), which are resident macrophages in the liver that serve as a major source of inflammatory cytokines; however, the association and the underlying mechanisms of KC functions in HS‑induced endotoxemia and inflammation require an improved understanding. The important chemokine macrophage inflammatory protein‑1α (MIP‑1α) increases inflammatory responses and the secretion of inflammatory molecules from KCs, including tumor necrosis factor‑α, interleukin (IL)‑1β and IL‑6...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28676010/kca3-1-channel-modulators-as-potential-therapeutic-compounds-for-glioblastoma
#12
Brandon M Brown, Brandon Pressley, Heike Wulff
The intermediate-conductance Ca2+-activated K+ channel KCa3.1 is widely expressed in cells of the immune system such as T- and B-lymphocytes, mast cells, macrophages and microglia, but also found in dedifferentiated vascular smooth muscle cells, fibroblasts and many cancer cells including pancreatic, prostate, leukemia and glioblastoma. In all these cell types KCa3.1 plays an important role in cellular activation, migration and proliferation by regulating membrane potential and Ca2+ signaling. KCa3.1 therefore constitutes an attractive therapeutic target for diseases involving excessive proliferation or activation of one more of these cell types and researchers both in academia and in the pharmaceutical industry have developed several potent and selective small molecule inhibitors of KCa3...
June 30, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28667557/atherosclerosis
#13
Mohammed Shamim Rahman, Kevin Woollard
In this chapter, we discuss the manner through which the immune system regulates the cardiovascular system in health and disease. We define the cardiovascular system and elements of atherosclerotic disease, the main focus in this chapter. Herein we elaborate on the disease process that can result in myocardial infarction (heart attack), ischaemic stroke and peripheral arterial disease. We have discussed broadly the homeostatic mechanisms in place that help autoregulate the cardiovascular system including the vital role of cholesterol and lipid clearance as well as the role lipid homeostasis plays in cardiovascular disease in the context of atherosclerosis...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28649610/evaluation-of-the-safety-and-immunomodulatory-effects-of-sargramostim-in-a-randomized-double-blind-phase-1-clinical-parkinson-s-disease-trial
#14
Howard E Gendelman, Yuning Zhang, Pamela Santamaria, Katherine E Olson, Charles R Schutt, Danish Bhatti, Bhagya Laxmi Dyavar Shetty, Yaman Lu, Katherine A Estes, David G Standaert, Elizabeth Heinrichs-Graham, LuAnn Larson, Jane L Meza, Matthew Follett, Erica Forsberg, Gary Siuzdak, Tony W Wilson, Carolyn Peterson, R Lee Mosley
A potential therapeutic role for immune transformation in Parkinson's disease evolves from more than a decade of animal investigations demonstrating regulatory T cell (Treg) nigrostriatal neuroprotection. To bridge these results to human disease, we conducted a randomized, placebo-controlled double-blind phase 1 trial with a well-studied immune modulator, sargramostim (granulocyte-macrophage colony-stimulating factor). We enrolled 17 age-matched non-Parkinsonian subjects as non-treated controls and 20 Parkinson's disease patients...
2017: NPJ Parkinson's Disease
https://www.readbyqxmd.com/read/28648478/imaging-vulnerable-plaques-by-targeting-inflammation-in-atherosclerosis-using-fluorescent-labeled-dual-ligand-microparticles-of-iron-oxide-and-magnetic-resonance-imaging
#15
Joyce M S Chan, Claudia Monaco, Marzena Wylezinska-Arridge, Jordi L Tremoleda, Jennifer E Cole, Michael Goddard, Maggie S H Cheung, Kishore K Bhakoo, Richard G J Gibbs
OBJECTIVE: Identification of patients with high-risk asymptomatic carotid plaques remains an elusive but essential step in stroke prevention. Inflammation is a key process in plaque destabilization and a prelude to clinical sequelae. There are currently no clinical imaging tools to assess the inflammatory activity within plaques. This study characterized inflammation in atherosclerosis using dual-targeted microparticles of iron oxide (DT-MPIO) as a magnetic resonance imaging (MRI) probe...
June 22, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28634421/the-role-of-von-willebrand-factor-in-vascular-inflammation-from-pathogenesis-to-targeted-therapy
#16
REVIEW
Felice Gragnano, Simona Sperlongano, Enrica Golia, Francesco Natale, Renatomaria Bianchi, Mario Crisci, Fabio Fimiani, Ivana Pariggiano, Vincenzo Diana, Andreina Carbone, Arturo Cesaro, Claudia Concilio, Giuseppe Limongelli, Mariagiovanna Russo, Paolo Calabrò
Beyond its role in hemostasis, von Willebrand factor (VWF) is an emerging mediator of vascular inflammation. Recent studies highlight the involvement of VWF and its regulator, ADAMTS13, in mechanisms that underlie vascular inflammation and immunothrombosis, like leukocyte rolling, adhesion, and extravasation; vascular permeability; ischemia/reperfusion injury; complements activation; and NETosis. The VWF/ADAMTS13 axis is implicated in the pathogenesis of atherosclerosis, promoting plaque formation and inflammation through macrophage and neutrophil recruitment in inflamed lesions...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28623120/association-between-ischemic-stroke-and-erdheim-chester-disease-a-case-report-and-review-of-literature
#17
Guillaume Fargeot, Sabrina Stefanizzi, Sebastien Depuydt, Frederic Klapczynski, Alain Ameri
Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis characterized by a xanthogranulomatous infiltration of tissues by spumous histiocytes. Neurological involvement is frequent, but ischemic strokes have been exceptionally described. We report the case of a 68-year-old woman who presented with an acute ischemic stroke associated with a multisystemic disorder including insipidus diabetes, infiltration of the aorta and the carotid arteries, perirenal infiltration, aortitis, and lytic bone lesions...
June 13, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28609584/endothelial-nitric-oxide-synthase-inhibition-triggers-inflammatory-responses-in-the-brain-of-male-rats-exposed-to-ischemia-reperfusion-injury
#18
Rosaria Greco, Chiara Demartini, Anna Maria Zanaboni, Fabio Blandini, Diana Amantea, Cristina Tassorelli
Nitric oxide (NO) derived from endothelial NO synthase (eNOS) plays a role in preserving and maintaining the brain's microcirculation, inhibiting platelet aggregation, leukocyte adhesion, and migration. Inhibition of eNOS activity results in exacerbation of neuronal injury after ischemia by triggering diverse cellular mechanisms, including inflammatory responses. To examine the relative contribution of eNOS in stroke-induced neuroinflammation, we analyzed the effects of systemic treatment with l-N-(1-iminoethyl)ornithine (L-NIO), a relatively selective eNOS inhibitor, on the expression of MiR-155-5p, a key mediator of innate immunity regulation and endothelial dysfunction, in the cortex of male rats subjected to transient middle cerebral artery occlusion (tMCAo) followed by 24 hr of reperfusion...
June 13, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28606360/sex-differences-in-regulatory-cells-in-experimental-stroke
#19
Hilary A Seifert, Gil Benedek, Jian Liang, Ha Nguyen, Gail Kent, Arthur A Vandenbark, Julie A Saugstad, Halina Offner
Stroke is the leading cause of disability in the United States. Sex differences, including smaller infarcts in females and greater involvement of immune-mediated inflammation in males may affect the efficacy of immune-modulating interventions. To address these differences, we sought to identify distinct stroke-modifying mechanisms in female vs. male mice. The current study demonstrated smaller infarcts and increased levels of regulatory CD19(+)CD5(+)CD1d(hi) B10 cells as well as anti-inflammatory CD11b(+)CD206(+) microglia/macrophages in the ipsilateral vs...
August 2017: Cellular Immunology
https://www.readbyqxmd.com/read/28603491/nosh-nbp-a-novel-nitric-oxide-and-hydrogen-sulfide-releasing-hybrid-attenuates-ischemic-stroke-induced-neuroinflammatory-injury-by-modulating-microglia-polarization
#20
Jing Ji, Pengjun Xiang, Tingting Li, Li Lan, Xiaole Xu, Guo Lu, Hui Ji, Yihua Zhang, Yunman Li
NOSH-NBP, a novel nitric oxide (NO) and hydrogen sulfide (H2S)-releasing hybrid, protects brain from ischemic stroke. This study mainly aimed to investigate the therapeutic effect of NOSH-NBP on ischemic stroke and the underlying mechanisms. In vivo, transient middle cerebral artery occlusion (tMCAO) was performed in C57BL/6 mice, with NO-NBP and H2S-NBP as controls. NO and H2S scavengers, carboxy-PTIO and BSS, respectively, were used to quench NO and H2S of NOSH-NBP. In vitro, BV2 microglia/BMDM were induced to the M1/2 phenotype, and conditioned medium (CM) experiments in BV2 microglia, neurons and b...
2017: Frontiers in Cellular Neuroscience
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