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Stroke immune suppression

Wei-Na Jin, Andrew F Ducruet, Qiang Liu, Samuel Xiang-Yu Shi, Michael Waters, Ming Zou, Kevin N Sheth, Rayna Gonzales, Fu-Dong Shi
Stroke-induced immune suppression predisposes the host to infections and can contribute to high morbidity and mortality in stroke patients. Because ischemic stroke has a profound effect on the systemic immune response, which may explain the increased susceptibility of stroke patients to infection, an urgent need persists for a better understanding of mechanisms associated with immune suppression; new and effective treatments for stroke can then be identified. NK cells play a key role in early host defense against pathogens by killing infected cells and/or producing cytokines such as IFN-γ...
January 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Alyce J Nicholls, Shu Wen Wen, Pam Hall, Michael J Hickey, Connie H Y Wong
Emerging evidence has revealed that noradrenaline (NA), the main neurotransmitter of the sympathetic nervous system (SNS), regulates a variety of immune functions via binding to adrenergic receptors present on immune cells. In this study, we examined the role of NA in the regulation of neutrophil functions. Neutrophils were isolated from the bone marrow of naïve mice and treated with NA at various concentrations to assess the effect on various neutrophil functions. Additionally, we performed cremaster intravital microscopy to examine neutrophil-endothelial cell interactions following NA superfusion in vivo...
December 21, 2017: Journal of Leukocyte Biology
Ami L DeWaters, Matthieu Chansard, Antonio Anzueto, Mary Jo Pugh, Eric M Mortensen
BACKGROUND: Major depressive disorder ("depression") has been identified as an independent risk factor for mortality for many comorbid conditions, including heart failure, cancer and stroke. Major depressive disorder has also been linked to immune suppression by generating a chronic inflammatory state. However, the association between major depression and pneumonia has not been examined. The aim of this study was to examine the association between depression and outcomes, including mortality and intensive care unit admission, in Veterans hospitalized with pneumonia...
January 2018: American Journal of the Medical Sciences
Zhiliang Guo, Shuhong Yu, Xin Chen, Ping Zheng, Ting Hu, Zhenhui Duan, Xiaoyun Liu, Qian Liu, Ruidong Ye, Wusheng Zhu, Xinfeng Liu
BACKGROUND: Inflammation and neutrophils play pivotal roles in hemorrhagic transformation (HT) after recombinant tissue plasminogen activator (rtPA) treatment in stroke; however, the contribution of Nod-like receptor protein 3 (NLRP3), a key component of the innate immune system, is not yet known. This study aimed to explore the role of NLRP3 in the delayed rtPA-induced HT and its association with the neutrophil recruitment. METHODS: Rats were subjected to thromboembolic focal cerebral ischemia and delayed rtPA treatment at 4 h after ischemia to mimic HT...
December 16, 2017: Brain Research Bulletin
Yuan Li, Bingzheng Lu, Longxiang Sheng, Zhu Zhu, Hongjiaqi Sun, Yuwei Zhou, Yang Yang, Dongdong Xue, Wenli Chen, Xuyan Tian, Yun Du, Min Yan, Wenbo Zhu, Fan Xing, Kai Li, Suizhen Lin, Pengxin Qiu, Xingwen Su, Yijun Huang, Guangmei Yan, Wei Yin
Hyperglycolysis, observed within the penumbra zone during brain ischemia, was shown to be detrimental for tissue survival because of lactate accumulation and reactive oxygen species overproduction in clinical and experimental settings. Recently, mounting evidence suggests that glycolytic reprogramming and induced metabolic enzymes can fuel the activation of peripheral immune cells. However, the possible roles and details regarding hyperglycolysis in neuroinflammation during ischemia are relatively poorly understood...
January 2018: Journal of Neurochemistry
Hye-Kyung Lee, Il-Doo Kim, Hahnbie Lee, Lidan Luo, Seung-Woo Kim, Ja-Kyeong Lee
It has been reported that the innate immune response plays important roles in brain ischemia and that the infiltration of blood-derived immune cells is a key initiator of this response. Nerve injury-induced protein 1 (Ninjurin 1, Ninj1) is a cell adhesion molecule responsible for cell-to-cell interactions between immune cells and endothelial cells. In the present study, we investigated the proinflammatory and neuroprotective effects of Ninj1 and a dodecamer peptide harboring Ninj1 N-terminal adhesion motif (N-NAM, Pro26~Asn37) in a rat middle cerebral artery occlusion (MCAO) model of stroke...
November 14, 2017: Molecular Neurobiology
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...
January 15, 2018: International Journal of Pharmaceutics
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...
February 2018: Experimental Neurology
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
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
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
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
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
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 nonpungent 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...
November 1, 2017: American Journal of Physiology. Endocrinology and Metabolism
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
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
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
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
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
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
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