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Stroke immune suppression

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https://www.readbyqxmd.com/read/29122608/thioredoxin-albumin-fusion-protein-prevents-copper-enhanced-zinc-induced-neurotoxicity-via-its-antioxidative-activity
#1
Ken-Ichiro Tanaka, Mikako Shimoda, Victor T G Chuang, Kento Nishida, Masahiro Kawahara, Tatsuhiro Ishida, Masaki Otagiri, Toru Maruyama, Yu Ishima
Zinc (Zn) is a co-factor for a vast number of enzymes, and functions as a regulator for immune mechanism and protein synthesis. However, excessive Zn release induced in pathological situations such as stroke or transient global ischemia is toxic. Previously, we demonstrated that the interaction of Zn and copper (Cu) is involved in the pathogenesis of Alzheimer's disease and vascular dementia. Furthermore, oxidative stress has been shown to play a significant role in the pathogenesis of various metal ions induced neuronal death...
November 6, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/29111308/inhibition-of-microrna-210-suppresses-pro-inflammatory-response-and-reduces-acute-brain-injury-of-ischemic-stroke-in-mice
#2
Lei Huang, Qingyi Ma, Yong Li, Bo Li, Lubo Zhang
Stroke is a leading cause of mortality and chronic neurologic disability. Yet, the successful treatment remains limited. In this study, we investigated the efficacy and the mechanism of a novel treatment, microRNA-210 (miR-210) inhibition, in protecting acute ischemic brain injury in adult mice. Focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) in adult male C57BL/6 mice. MiR-210-LNA (miR-210 inhibitor) or the negative control was administered via intracerebroventricular injection 24h prior or 4h after MCAO...
October 27, 2017: Experimental Neurology
https://www.readbyqxmd.com/read/29110213/correction-to-neuroimmune-response-in-ischemic-preconditioning
#3
Ashley McDonough, Jonathan R Weinstein
Ischemic preconditioning (IPC) is a robust neuroprotective phenomenon in which a brief period of cerebral ischemia confers transient tolerance to subsequent ischemic challenge. Research on IPC has implicated cellular, molecular, and systemic elements of the immune response in this phenomenon. Potent molecular mediators of IPC include innate immune signaling pathways such as Toll-like receptors and type 1 interferons. Brain ischemia results in release of pro- and anti-inflammatory cytokines and chemokines that orchestrate the neuroinflammatory response, resolution of inflammation, and transition to neurological recovery and regeneration...
November 6, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
https://www.readbyqxmd.com/read/29063799/genistein-mechanisms-of-action-for-a-pleiotropic-neuroprotective-agent-in-stroke
#4
Derek A Schreihofer, Anthony Oppong-Gyebi
Genistein is a plant estrogen promoted as an alternative to post-menopausal hormone therapy because of a good safety profile and its promotion as a natural product. Several preclinical studies of cerebral ischemia and other models of brain injury support a beneficial role for genistein in protecting the brain from injury whether administered chronically or acutely. Like estrogen, genistein is a pleiotropic molecule that engages several different mechanisms to enhance brain health, including reduction of oxidative stress, promotion of growth factor signaling, and immune suppression...
October 24, 2017: Nutritional Neuroscience
https://www.readbyqxmd.com/read/29021532/monocyte-lymphocyte-cross-communication-via-soluble-cd163-directly-links-innate-immune-system-activation-and-adaptive-immune-system-suppression-following-ischemic-stroke
#5
Grant C O'Connell, Connie S Tennant, Noelle Lucke-Wold, Yasser Kabbani, Abdul R Tarabishy, Paul D Chantler, Taura L Barr
CD163 is a scavenger receptor expressed on innate immune cell populations which can be shed from the plasma membrane via the metalloprotease ADAM17 to generate a soluble peptide with lympho-inhibitory properties. The purpose of this study was to investigate CD163 as a possible effector of stroke-induced adaptive immune system suppression. Liquid biopsies were collected from ischemic stroke patients (n = 39), neurologically asymptomatic controls (n = 20), and stroke mimics (n = 20) within 24 hours of symptom onset...
October 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28855861/regulation-of-microglia-and-macrophage-polarization-via-apoptosis-signal-regulating-kinase-1-silencing-after-ischemic-hypoxic-injury
#6
So Yeong Cheon, Eun Jung Kim, Jeong Min Kim, Eun Hee Kam, Byung Woong Ko, Bon-Nyeo Koo
Inflammation is implicated in ischemic stroke and is involved in abnormal homeostasis. Activation of the immune system leads to breakdown of the blood-brain barrier and, thereby, infiltration of immune cells into the brain. Upon cerebral ischemia, infiltrated macrophages and microglia (resident CNS immune cell) are activated, change their phenotype to M1 or M2 based on the microenvironment, migrate toward damaged tissue, and are involved in repair or damage. Those of M1 phenotype release pro-inflammatory mediators, which are associated with tissue damage, while those of M2 phenotype release anti-inflammatory mediators, which are related to tissue recovery...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28811825/ethanol-extract-of-mylabris-phalerata-inhibits-m2-polarization-induced-by-recombinant-il-4-and-il-13-in-murine-macrophages
#7
Hwan-Suck Chung, Bong-Seon Lee, Jin Yeul Ma
Mylabris phalerata (MP) is an insect used in oriental herbal treatments for tumor, tinea infections, and stroke. Recent studies have shown that tumor-associated macrophages (TAM) have detrimental roles such as tumor progression, angiogenesis, and metastasis. Although TAM has phenotypes and characteristics in common with M2-polarized macrophages, M1 macrophages have tumor suppression and immune stimulation effects. Medicines polarizing macrophages to M1 have been suggested to have anticancer effects via the modulation of the tumor microenvironment...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28811294/dihydrocapsiate-improved-age-associated-impairments-in-mice-by-increasing-energy-expenditure
#8
Kana Ohyama, Katsuya Suzuki
Metabolic dysfunction is associated with aging and results in age-associated chronic diseases, including type 2 diabetes mellitus, cardiovascular disease, and stroke. Hence, there has been a focus on increasing energy expenditure in aged populations to protect them from age-associated diseases. Dihydrocapsiate (DCT) is a compound that belongs to the capsinoid family. Capsinoids are capsaicin analogs that are found in non-pungent peppers and increase whole-body energy expenditure. However, their effect on energy expenditure has been reported only in young populations, and to date the effectiveness of DCT in increasing energy expenditure in aged populations has not been investigated...
August 15, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28736792/double-injected-human-stem-cells-enhance-rehabilitation-in-tbi-mice-via-modulation-of-survival-and-inflammation
#9
Chul Kim, Ji-Min Park, TaeHo Kong, Seungmin Lee, Ki-Weon Seo, Yuri Choi, Young Sook Song, Jisook Moon
Traumatic brain injury (TBI), a complicated form of brain damage, is a major cause of mortality in adults. Following mechanical and structural primary insults, a battery of secondary insults, including neurotransmitter-mediated cytotoxicity, dysregulation of calcium and macromolecule homeostasis, and increased oxidative stress, exacerbate brain injury and functional deficits. Although stem cell therapy is considered to be an alternative treatment for brain injuries, such as TBI and stroke, many obstacles remain...
July 24, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28645895/multiparity-improves-outcomes-after-cerebral-ischemia-in-female-mice-despite-features-of-increased-metabovascular-risk
#10
Rodney M Ritzel, Anita R Patel, Monica Spychala, Rajkumar Verma, Joshua Crapser, Edward C Koellhoffer, Anna Schrecengost, Evan R Jellison, Liang Zhu, Venugopal Reddy Venna, Louise D McCullough
Females show a varying degree of ischemic sensitivity throughout their lifespan, which is not fully explained by hormonal or genetic factors. Epidemiological data suggest that sex-specific life experiences such as pregnancy increase stroke risk. This work evaluated the role of parity on stroke outcome. Age-matched virgin (i.e., nulliparous) and multiparous mice were subjected to 60 min of reversible middle cerebral artery occlusion and evaluated for infarct volume, behavioral recovery, and inflammation. Using an established mating paradigm, fetal microchimeric cells present in maternal mice were also tracked after parturition and stroke...
July 11, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28592261/trem2-protects-against-cerebral-ischemia-reperfusion-injury
#11
Rong Wu, Xiangpen Li, Pengfei Xu, Likui Huang, Jinping Cheng, Xiaolong Huang, Jingru Jiang, Long-Jun Wu, Yamei Tang
Although post-ischemic inflammation induced by the innate immune response is considered an essential step in the progression of cerebral ischemia injury, the role of triggering receptor expressed on myeloid cells 2 (TREM2) in the pathogenesis of ischemic stroke remains to be elucidated. Here, we found that the transcriptional and post-transcriptional levels of TREM2 were increased in cultured primary microglia after oxygen-glucose deprivation and reoxygenation and in the ischemic penumbra of the cerebral cortex after middle cerebral artery occlusion (MCAO) and reperfusion in mice...
June 7, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28535201/regulatory-t-cells-ameliorate-tissue-plasminogen-activator-induced-brain-haemorrhage-after-stroke
#12
Leilei Mao, Peiying Li, Wen Zhu, Wei Cai, Zongjian Liu, Yanling Wang, Wenli Luo, Ruth A Stetler, Rehana K Leak, Weifeng Yu, Yanqin Gao, Jun Chen, Gang Chen, Xiaoming Hu
Delayed thrombolytic treatment with recombinant tissue plasminogen activator (tPA) may exacerbate blood-brain barrier breakdown after ischaemic stroke and lead to lethal haemorrhagic transformation. The immune system is a dynamic modulator of stroke response, and excessive immune cell accumulation in the cerebral vasculature is associated with compromised integrity of the blood-brain barrier. We previously reported that regulatory T cells, which function to suppress excessive immune responses, ameliorated blood-brain barrier damage after cerebral ischaemia...
July 1, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/28469772/epo-cyclosporine-combination-therapy-reduced-brain-infarct-area-in-rat-after-acute-ischemic-stroke-role-of-innate-immune-inflammatory-response-micro-rnas-and-mapk-family-signaling-pathway
#13
Chun-Man Yuen, Kuo-Ho Yeh, Christopher Glenn Wallace, Kuan-Hung Chen, Hung-Sheng Lin, Pei-Hsun Sung, Han-Tan Chai, Yung-Lung Chen, Cheuk-Kwan Sun, Chih-Hung Chen, Gour-Shenq Kao, Sheung-Fat Ko, Hon-Kan Yip
This study tested the hypothesis that erythropoietin (EPO) and cyclosporine (CsA) could effectively reduce brain infarct area (BIA) in rat after acute ischemic stroke (AIS) through regulating inflammation, oxidative stress, MAPK family signaling and microRNA (miR-223/miR-30a/miR-383). Adult male Sprague-Dawley rats (n = 48) were equally divided into group 1 (sham control), group 2 (AIS), group 3 [AIS+EPO (5,000 IU/kg at 0.5/24/48 h, subcutaneous)] and group 4 [AIS+CsA (20.0 mg/kg at 0.5/24/48 h, intra-peritoneal)]...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28314594/brain-ischemia-suppresses-immunity-in-the-periphery-and-brain-via-different-neurogenic-innervations
#14
Qiang Liu, Wei-Na Jin, Yaou Liu, Kaibin Shi, Haoran Sun, Fang Zhang, Chao Zhang, Rayna J Gonzales, Kevin N Sheth, Antonio La Cava, Fu-Dong Shi
Brain ischemia inhibits immune function systemically, with resulting infectious complications. Whether in stroke different immune alterations occur in brain and periphery and whether analogous mechanisms operate in these compartments remains unclear. Here we show that in patients with ischemic stroke and in mice subjected to middle cerebral artery occlusion, natural killer (NK) cells display remarkably distinct temporal and transcriptome profiles in the brain as compared to the periphery. The activation of catecholaminergic and hypothalamic-pituitary-adrenal axis leads to splenic atrophy and contraction of NK cell numbers in the periphery through a modulated expression of SOCS3, whereas cholinergic innervation-mediated suppression of NK cell responses in the brain involves RUNX3...
March 21, 2017: Immunity
https://www.readbyqxmd.com/read/28255762/semax-an-analog-of-acth-4-7-regulates-expression-of-immune-response-genes-during-ischemic-brain-injury-in-rats
#15
Ekaterina V Medvedeva, Veronika G Dmitrieva, Svetlana A Limborska, Nikolay F Myasoedov, Lyudmila V Dergunova
Brain stroke continues to claim the lives of million people every year. To build the effective strategies for stroke treatment it is necessary to understand the neuroprotective mechanisms that are able to prevent the ischemic injury. Consisting of the ACTH(4-7) fragment and the tripeptide Pro-Gly-Pro (PGP), the synthetic peptide Semax effectively protects brain against ischemic stroke. However, the molecular mechanisms underlying its neuroprotection and participation of PGP in them are still needed to be clarified...
June 2017: Molecular Genetics and Genomics: MGG
https://www.readbyqxmd.com/read/28155572/exploring-the-role-of-microglia-in-cortical-spreading-depression-in-neurological-disease
#16
REVIEW
Mamoru Shibata, Norihiro Suzuki
Microglia play a pivotal role in innate immunity in the brain. During development, they mature from myeloerythroid progenitor cells in the yolk sac and colonize the brain to establish a resident population of tissue macrophages. In the postnatal brain, they exert phagocytosis and induce inflammatory response against invading pathogens. Microglia also act as guardians of brain homeostasis by surveying the microenvironment using motile processes. Cortical spreading depression (CSD) is a slowly propagating (2-5 mm/min) wave of rapid, near-complete depolarization of neurons and astrocytes followed by a period of electrical suppression of a distinct population of cortical neurons...
April 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28154551/prolonged-activation-of-invariant-natural-killer-t-cells-and-th2-skewed-immunity-in-stroke-patients
#17
Connie H Y Wong, Craig N Jenne, Patrick P Tam, Caroline Léger, Andres Venegas, Karla Ryckborst, Michael D Hill, Paul Kubes
BACKGROUND: Infection is highly prevalent and contribute significantly to mortality of stroke patients. In addition to the well described robust systemic lymphocytopenia and skewed T helper 2 (TH2)-immunity after stroke, emerging experimental evidence demonstrate that the development of infection poststroke is attributed by the activation of invariant natural killer T (iNKT) cells. In this prospective study, we examined the levels of a broad spectrum of inflammatory mediators, the activation status of iNKT cell in the blood of patients with various degree of stroke severity, and investigate whether these parameters differ in patients who later develop poststroke infections...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28132764/3h-1-2-dithiole-3-thione-as-a-novel-therapeutic-agent-for-the-treatment-of-ischemic-stroke-through-nrf2-defense-pathway
#18
Ping-Chang Kuo, I-Chen Yu, Barbara A Scofield, Dennis A Brown, Eric T Curfman, Hallel C Paraiso, Fen-Lei Chang, Jui-Hung Yen
Cerebral ischemic stroke accounts for more than 80% of all stroke cases. During cerebral ischemia, reactive oxygen species produced in brain tissue induce oxidative stress and inflammatory responses. D3T, the simplest compound of the cyclic, sulfur-containing dithiolethiones, is found in cruciferous vegetables and has been reported to induce antioxidant genes and glutathione biosynthesis through activation of Nrf2. In addition to antioxidant activity, D3T was also reported to possess anti-inflammatory effects...
January 26, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/27923376/immunomodulation-after-ischemic-stroke-potential-mechanisms-and-implications-for-therapy
#19
REVIEW
Cynthia Santos Samary, Paolo Pelosi, Pedro Leme Silva, Patricia Rieken Macedo Rocco
Brain injuries are often associated with intensive care admissions, and carry high morbidity and mortality rates. Ischemic stroke is one of the most frequent causes of injury to the central nervous system. It is now increasingly clear that human stroke causes multi-organ systemic disease. Brain inflammation may lead to opposing local and systemic effects. Suppression of systemic immunity by the nervous system could protect the brain from additional inflammatory damage; however, it may increase the susceptibility to infection...
December 7, 2016: Critical Care: the Official Journal of the Critical Care Forum
https://www.readbyqxmd.com/read/27861531/macrophage-derived-angiopoietin-like-protein-2-exacerbates-brain-damage-by-accelerating-acute-inflammation-after-ischemia-reperfusion
#20
Toshihiro Amadatsu, Jun Morinaga, Takayuki Kawano, Kazutoyo Terada, Tsuyoshi Kadomatsu, Keishi Miyata, Motoyoshi Endo, Daiki Kasamo, Jun-Ichi Kuratsu, Yuichi Oike
Ischemic stroke is a leading cause of death and disability worldwide. Several reports suggest that acute inflammation after ischemia-reperfusion exacerbates brain damage; however, molecular mechanisms underlying this effect remain unclear. Here, we report that MAC-3-positive immune cells, including infiltrating bone marrow-derived macrophages and activated microglia, express abundant angiopoietin-like protein (ANGPTL) 2 in ischemic mouse brain in a transient middle cerebral artery occlusion (MCAO) model. Both neurological deficits and infarct volume decreased in transient MCAO model mice established in Angptl2 knockout (KO) relative to wild-type mice...
2016: PloS One
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