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https://www.readbyqxmd.com/read/28523230/targeting-resolution-of-neuroinflammation-after-ischemic-stroke-with-a-lipoxin-a4-analog-protective-mechanisms-and-long-term-effects-on-neurological-recovery
#1
Kimberly E Hawkins, Kelly M DeMars, Jon C Alexander, Lauren G de Leon, Sean C Pacheco, Christina Graves, Changjun Yang, Austin O McCrea, Jan C Frankowski, Timothy J Garrett, Marcelo Febo, Eduardo Candelario-Jalil
BACKGROUND: Resolution of inflammation is an emerging new strategy to reduce damage following ischemic stroke. Lipoxin A4 (LXA 4) is an anti-inflammatory, pro-resolution lipid mediator that reduces neuroinflammation in stroke. Since LXA 4 is rapidly inactivated, potent analogs have been synthesized, including BML-111. We hypothesized that post-ischemic, intravenous treatment with BML-111 for 1 week would provide neuroprotection and reduce neurobehavioral deficits at 4 weeks after ischemic stroke in rats...
May 2017: Brain and Behavior
https://www.readbyqxmd.com/read/28517732/t-cells-and-macrophages-peak-weeks-after-experimental-stroke-spatial-and-temporal-characteristics
#2
Nina Vindegaard, Clara Muñoz-Briones, Henrik H El Ali, Lotte Kellemann Kristensen, Rune Skovgaard Rasmussen, Flemming Fryd Johansen, Henrik Hasseldam
The activities of the central and peripheral immune systems impact neurological outcome after ischemic stroke. However, studies investigating the temporal profile of leukocyte infiltration, especially T-cell recruitment, are sparse. Our aim was to investigate leukocyte infiltration at different time points after experimental stroke in mice. Permanent middle cerebral artery occlusion was performed on 11 weeks old C57BL/6J mice, allowed to survive for 1, 3, 8, 14 or 28 days. In addition to infarct size measurements, detailed immunohistochemical analyses of T-cell and macrophage influx were performed...
May 18, 2017: Neuropathology: Official Journal of the Japanese Society of Neuropathology
https://www.readbyqxmd.com/read/28487994/cd74-immunoreactive-activated-m1-microglia-are-shown-late-in-the-gerbil-hippocampal-ca1-region-following-transient-cerebral-ischemia
#3
In Koo Hwang, Joon Ha Park, Tae-Kyeong Lee, Dae Won Kim, Ki-Yeon Yoo, Ji Hyeon Ahn, Yang Hee Kim, Jun Hwi Cho, Young-Myeong Kim, Moo-Ho Won, Seung Myung Moon
Activated M1 microglia secrete proinflammatory cytokines into damaged brain areas. The present study examined activated M1 microglial morphology and expression in the hippocampal Cornu Ammonis (CA) 1 region, which is vulnerable to transient ischemia. Transient cerebral ischemia was performed for 5 min in gerbils, and neuronal death in the CA1 region following transient cerebral ischemia was confirmed using cresyl violet staining, neuronal nuclear antigen immunohistochemistry and Fluoro‑Jade B histofluorescent staining...
June 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28482260/increased-expression-of-tfpi-in-human-carotid-stenosis
#4
Benedicte Stavik, Sverre Holm, Sandra Espada, Nina Iversen, Bjørnar Sporsheim, Vigdis Bjerkeli, Tuva Børresdatter Dahl, Per Morten Sandset, Mona Skjelland, Terje Espevik, Grethe Skretting, Bente Halvorsen
INTRODUCTION: Tissue factor (TF) pathway inhibitor (TFPI) is the physiological inhibitor of TF induced blood coagulation and two isoforms exists, TFPIα and TFPIβ. In atherosclerotic plaques, TFPI may inhibit TF activity and thrombus formation, which is the main cause of ischemic stroke in carotid artery disease. We aimed to identify the isoforms of TFPI present in human carotid plaques and potential sources of TFPI. MATERIALS AND METHODS: Human atherosclerotic plaques from carotid endarterectomies were used for mRNA and immunohistochemistry analyses...
April 28, 2017: Thrombosis Research
https://www.readbyqxmd.com/read/28471481/cytotoxic-lymphocytes-and-atherosclerosis-significance-mechanisms-and-therapeutic-challenges
#5
Tin Kyaw, Karlheinz Peter, Li Yi, Peter Tipping, Ban-Hock Toh, Alex Bobik
Cytotoxic lymphocytes encompass natural killer (NK) lymphocytes (cells) and cytotoxic T cells that include CD8+ T cells, NKT cells, gamma, delta (γδ)-T cells and human CD4 + CD28- T cells. These cells play critical roles in inflammatory diseases and in controlling cancers and infections. Cytotoxic lymphocytes can be activated via a number of mechanisms that may involve dendritic cells, macrophages, cytokines or surface proteins on stressed cells. Upon activation, they secrete proinflammatory cytokines as well as anti-inflammatory cytokines, chemokines and cytotoxins to promote inflammation and development of atherosclerotic lesions including vulnerable lesions, which are strongly implicated in myocardial infarctions and strokes...
May 4, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28413029/evidence-for-the-involvement-of-matrix-degrading-metalloproteinases-mmps-in-atherosclerosis
#6
Bethan A Brown, Helen Williams, Sarah J George
Atherosclerosis leads to blockage of arteries, culminating in myocardial infarction, and stroke. The involvement of matrix-degrading metalloproteinases (MMPs) in atherosclerosis is established and many studies have highlighted the importance of various MMPs in this process. MMPs were first implicated in atherosclerosis due to their ability to degrade extracellular matrix components, which can lead to increased plaque instability. However, more recent work has highlighted a multitude of roles for MMPs in addition to breakdown of extracellular matrix proteins...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28392564/the-immunology-of-atherosclerosis
#7
REVIEW
Anton Gisterå, Göran K Hansson
Cardiovascular disease is the leading cause of death worldwide, both in the general population and among patients with chronic kidney disease (CKD). In most cases, the underlying cause of the cardiovascular event is atherosclerosis - a chronic inflammatory disease. CKD accelerates atherosclerosis via augmentation of inflammation, perturbation of lipid metabolism, and other mechanisms. In the artery wall, subendothelial retention of plasma lipoproteins triggers monocyte-derived macrophages and T helper type 1 (TH1) cells to form atherosclerotic plaques...
June 2017: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/28389473/st2-il-33-dependent-microglial-response-limits-acute-ischemic-brain-injury
#8
Yuanyuan Yang, Huan Liu, Haiyue Zhang, Qing Ye, Jianyi Wang, Boyu Yang, Leilei Mao, Wen Zhu, Rehana K Leak, Bo Xiao, Binfeng Lu, Jun Chen, Xiaoming Hu
ST2, a member of the interleukin (IL) 1 receptor family, and its ligand IL-33 play critical roles in immune regulation and inflammatory responses. This study explores the roles of endogenous IL-33/ST2 signaling in ischemic brain injury and elucidates the underlying mechanisms of action. The expression of IL-33 rapidly increased in oligodendrocytes and astrocytes after 60 min transient middle cerebral artery occlusion (tMCAO). ST2 receptor deficiency exacerbated brain infarction 3 d after tMCAO as well as distal permanent MCAO...
May 3, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28385306/detection-of-atherosclerotic-inflammation-by-68-ga-dotatate-pet-compared-to-18-f-fdg-pet-imaging
#9
Jason M Tarkin, Francis R Joshi, Nicholas R Evans, Mohammed M Chowdhury, Nichola L Figg, Aarti V Shah, Lakshi T Starks, Abel Martin-Garrido, Roido Manavaki, Emma Yu, Rhoda E Kuc, Luigi Grassi, Roman Kreuzhuber, Myrto A Kostadima, Mattia Frontini, Peter J Kirkpatrick, Patrick A Coughlin, Deepa Gopalan, Tim D Fryer, John R Buscombe, Ashley M Groves, Willem H Ouwehand, Martin R Bennett, Elizabeth A Warburton, Anthony P Davenport, James H F Rudd
BACKGROUND: Inflammation drives atherosclerotic plaque rupture. Although inflammation can be measured using fluorine-18-labeled fluorodeoxyglucose positron emission tomography ([(18)F]FDG PET), [(18)F]FDG lacks cell specificity, and coronary imaging is unreliable because of myocardial spillover. OBJECTIVES: This study tested the efficacy of gallium-68-labeled DOTATATE ((68)Ga-DOTATATE), a somatostatin receptor subtype-2 (SST2)-binding PET tracer, for imaging atherosclerotic inflammation...
April 11, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28377485/ischemic-cerebroprotection-conferred-by-myeloid-lineage-restricted-or-global-cd39-transgene-expression
#10
Amy E Baek, Nadia R Sutton, Danica Petrovic-Djergovic, Hui Liao, Jessica Ray, Joan Park, Yogendra Kanthi, David J Pinsky
Background -Cerebral tissue damage after an ischemic event can be exacerbated by inflammation and thrombosis. Elevated extracellular ATP and ADP levels are associated with cellular injury, inflammation and thrombosis. Ectonucleoside triphosphate diphosphohydrolase-1 (CD39), an enzyme expressed on the plasmalemma of leukocytes and endothelial cells, suppresses platelet activation and leukocyte infiltration by phosphohydrolyzing ATP/ADP. To investigate the effects of increased CD39 in an in vivo cerebral ischemia model, we developed a transgenic (TG) mouse expressing human CD39 (hCD39)...
April 4, 2017: Circulation
https://www.readbyqxmd.com/read/28366792/serum-macrophage-migration-inhibitory-factor-concentrations-correlate-with-prognosis-of-traumatic-brain-injury
#11
Ding-Bo Yang, Wen-Hua Yu, Xiao-Qiao Dong, Zu-Yong Zhang, Quan Du, Qiang Zhu, Zhi-Hao Che, Hao Wang, Yong-Feng Shen, Li Jiang
BACKGROUND: Macrophage migration inhibitory factor (MIF) is a well-known pro-inflammatory cytokine. Serum MIF concentrations are associated with the severity and prognosis of ischemic stroke. METHODS: In this prospective, observational study, white blood cell (WBC) count and serum concentrations of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α) and MIF among 108 severe traumatic brain injury (TBI) patients and 108 controls were measured...
March 30, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28323006/the-role-of-sumoylation-in-cerebral-hypoxia-and-ischemia
#12
REVIEW
Myriam Peters, Betty Wielsch, Johannes Boltze
The process of protein modification by adding or detaching small ubiquitin-like modifiers (SUMO) proteins, called SUMOylation, contributes to the regulation of numerous processes in eukaryotic cells. SUMOylation also represents a key response and adaption mechanism to different forms of metabolic stress. The central nervous system (CNS) and neurons in particular are highly susceptible to hypoxic-ischemic stress due to the lack of significant oxygen and energy reserves. SUMOylation is observed in many molecular responses to metabolic stress in the brain, and is therefore supposed to represent an endogenous neuroprotective mechanism...
March 17, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28303450/dr%C3%AE-1-mog-35-55-treatment-reduces-lesion-volumes-and-improves-neurological-deficits-after-traumatic-brain-injury
#13
Liu Yang, Zhijia Liu, Honglei Ren, Lei Zhang, Siman Gao, Li Ren, Zhi Chai, Roberto Meza-Romero, Gil Benedek, Arthur A Vandenbark, Halina Offner, Minshu Li
Traumatic brain injury (TBI) results in severe neurological impairments without effective treatments. Inflammation appears to be an important contributor to key pathogenic events such as secondary brain injury following TBI and therefore serves as a promising target for novel therapies. We have recently demonstrated the ability of a molecular construct comprised of the human leukocyte antigen (HLA)-DRα1 domain linked covalently to mouse (m)MOG-35-55 peptide (DRα1-MOG-35-55 construct) to reduce CNS inflammation and tissue injury in animal models of multiple sclerosis and ischemic stroke...
March 16, 2017: Metabolic Brain Disease
https://www.readbyqxmd.com/read/28292872/targeting-different-monocyte-macrophage-subsets-has-no-impact-on-outcome-in-experimental-stroke
#14
Antje Schmidt, Jan-Kolja Strecker, Stephanie Hucke, Nils-Martin Bruckmann, Martin Herold, Matthias Mack, Kai Diederich, Wolf-Rüdiger Schäbitz, Heinz Wiendl, Luisa Klotz, Jens Minnerup
BACKGROUND AND PURPOSE: Peripheral immune cell infiltration contributes to neural injury after ischemic stroke. However, in contrast to lymphocytes and neutrophils, the role of different monocyte/macrophage subsets remains to be clarified. Therefore, we evaluated the effects of selective and unselective monocyte/macrophage depletion and proinflammatory (M1-) and anti-inflammatory (M2-) macrophage transfer on the outcome after experimental cerebral ischemia. METHODS: To assess short-term effects of monocytes/macrophages in acute ischemic stroke, mice underwent transient middle cerebral artery occlusion and received either clodronate liposomes for unselective macrophage depletion, MC-21-antibody for selective depletion of proinflammatory Ly-6C(high) monocytes, or proinflammatory (M1-) or anti-inflammatory (M2-) macrophage transfer...
March 14, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/28265034/extracellular-matrix-inflammation-in-vascular-cognitive-impairment-and-dementia
#15
REVIEW
Gary A Rosenberg
Vascular cognitive impairment and dementia (VCID) include a wide spectrum of chronic manifestations of vascular disease related to large vessel strokes and small vessel disease (SVD). Lacunar strokes and white matter (WM) injury are consequences of SVD. The main vascular risk factor for SVD is brain hypoperfusion from cerebral blood vessel narrowing due to chronic hypertension. The hypoperfusion leads to activation and degeneration of astrocytes with the resulting fibrosis of the extracellular matrix (ECM)...
March 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28260801/regulation-of-microglial-activation-in-stroke
#16
REVIEW
Shou-Cai Zhao, Ling-Song Ma, Zhao-Hu Chu, Heng Xu, Wen-Qian Wu, Fudong Liu
When ischemic stroke occurs, oxygen and energy depletion triggers a cascade of events, including inflammatory responses, glutamate excitotoxicity, oxidative stress, and apoptosis that result in a profound brain injury. The inflammatory response contributes to secondary neuronal damage, which exerts a substantial impact on both acute ischemic injury and the chronic recovery of the brain function. Microglia are the resident immune cells in the brain that constantly monitor brain microenvironment under normal conditions...
April 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28258674/ibudilast-a-non%C3%A2-selective-phosphodiesterase-inhibitor-in-brain-disorders
#17
Joanna Schwenkgrub, Małgorzata Zaremba, Dagmara Mirowska-Guzel, Iwona Kurkowska-Jastrzębska
Ibudilast (IBD) is a non‑selective (3, 4, 10, 11) phosphodiesterase (PDE) inhibitor, used mainly as a bronchodilator for the treatment of bronchial asthma. PDE play a central role in cellular function (e.g. differentiation, synaptic plasticity and inflammatory response) by metabolizing cyclic nucleotides. The results from preclinical and clinical studies indicate that IBD has a broader range of action through suppression of pro‑inflammatory cytokines (IL‑6, IL‑1β, TNF‑α), toll‑like receptor 4 blockade (TLR‑4), inhibition of a macrophage migration inhibitory factor (MIF), up‑regulation the anti‑inflammatory cytokine (IL‑10), and promotion of neurotrophic factors (GDNF, NGF, NT‑4)...
March 2, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28253906/molecular-imaging-of-nestin-in-neuroinflammatory-conditions-reveals-marked-signal-induction-in-activated-microglia
#18
Senthil Krishnasamy, Yuan-Cheng Weng, Sai Sampath Thammisetty, Daniel Phaneuf, Melanie Lalancette-Hebert, Jasna Kriz
BACKGROUND: Nestin is a known marker of neuronal progenitor cells in the adult brain. Following neuro- and gliogenesis, nestin is replaced by cell type-specific intermediate filaments, e.g., neurofilaments for panneuronal expression and glial fibrillary acidic protein as a specific marker of mature astrocytes. While previous work have been mostly focused on the neuronal fate of nestin-positive progenitors, in the present study, we sought to investigate in real time how nestin signals and cellular expression patterns are controlled in the context of neuroinflammatory challenge and ischemic brain injury...
March 3, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28245599/complex-roles-of-microglial-cells-in-ischemic-stroke-pathobiology-new-insights-and-future-directions
#19
REVIEW
Revathy Guruswamy, Ayman ElAli
Ischemic stroke constitutes the major cause of death and disability in the industrialized world. The interest in microglia arose from the evidence outlining the role of neuroinflammation in ischemic stroke pathobiology. Microglia constitute the powerhouse of innate immunity in the brain. Microglial cells are highly ramified, and use these ramifications as sentinels to detect changes in brain homeostasis. Once a danger signal is recognized, cells become activated and mount specialized responses that range from eliminating cell debris to secreting inflammatory signals and trophic factors...
February 25, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28210215/tryptanthrin-suppresses-the-activation-of-the-lps-treated-bv2-microglial-cell-line-via-nrf2-ho-1-antioxidant-signaling
#20
Young-Won Kwon, So Yeong Cheon, Sung Yun Park, Juhyun Song, Ju-Hee Lee
Microglia are the resident macrophages in the central nervous system (CNS) and play essential roles in neuronal homeostasis and neuroinflammatory pathologies. Recently, microglia have been shown to contribute decisively to neuropathologic processes after ischemic stroke. Furthermore, natural compounds have been reported to attenuate inflammation and pathologies associated with neuroinflammation. Tryptanthrin (indolo[2,1-b]quinazoline-6,12-dione) is a phytoalkaloid with known anti-inflammatory effects in cells...
2017: Frontiers in Cellular Neuroscience
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