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Stroke immune suppression

Ruihe Lin, Jingli Cai, Eric W Kostuk, Robert Rosenwasser, Lorraine Iacovitti
BACKGROUND: Dimethyl fumarate (DMF), working via its metabolite monomethylfumarate (MMF), acts as a potent antioxidant and immunomodulator in animal models of neurologic disease and in patients with multiple sclerosis. These properties and their translational potential led us to investigate whether DMF/MMF could also protect at-risk and/or dying neurons in models of ischemic stroke in vitro and in vivo. Although the antioxidant effects have been partially addressed, the benefits of DMF immunomodulation after ischemic stroke still need to be explored...
October 13, 2016: Journal of Neuroinflammation
Willeke F Westendorp, Jan-Dirk Vermeij, Matthijs C Brouwer, Y B W E M Roos, Paul J Nederkoorn, Diederik van de Beek
BACKGROUND: Stroke-associated infections occur frequently and are associated with unfavorable outcome. Previous cohort studies suggest a protective effect of beta-blockers (BBs) against infections. A sympathetic drive may increase immune suppression and infections. AIM: This study is aimed at investigating the association between BB treatment at baseline and post-stroke infection in the Preventive Antibiotics in Stroke Study (PASS), a prospective clinical trial...
October 5, 2016: Cerebrovascular Diseases
Hye-Seon Jung, Si-Yeon Jeong, Jiwon Yang, So-Dam Kim, Baojin Zhang, Hyun Seung Yoo, Sun U Song, Myung-Shin Jeon, Yun Seon Song
Bone marrow-derived mesenchymal stem cells (MSCs) are used in stroke treatment despite the poor understanding of its mode of action. The immune suppressive and anti-inflammatory properties of MSCs possibly play important roles in regulating neuroinflammation after stroke. We investigated whether MSCs reduce the inflammatory complement component 3 (C3) levels, thus, providing neuroprotection during stroke. Mice were subjected to transient focal cerebral ischemia (tFCI), after which MSCs were intravenously injected...
October 28, 2016: Neuroscience Letters
Chun-Ye Ma, Lin Yin
Angiotensin II type 2 receptor (AT2R) activation has been shown to protect against stroke, but its precise mechanism remains poorly understood. We investigated whether the protective effect of AT2R against ischemia/reperfusion injury is mediated by the suppression of immune and inflammatory responses. Rat models of middle cerebral artery occlusion were intraperitoneally injected with physiological saline, the AT2R agonist CGP42112 (1 mg/kg per day) or antagonist PD123319 (1 mg/kg per day). In the CGP42112 group, AT2R expression increased, the infarct area decreased, interleukin-1β and tumor necrosis factor-α expression decreased, and interleukin-10 expression increased compared with the saline group...
July 2016: Neural Regeneration Research
Dallas Jones, Anna Blackmon, C Preston Neff, Brent E Palmer, Don Gilden, Hussain Badani, Maria A Nagel
: Varicella zoster virus (VZV) vasculopathy produces stroke, giant cell arteritis and granulomatous aortitis and develops after virus reactivates from ganglia and spreads transaxonally to arterial adventitia, resulting in persistent inflammation and pathological vascular remodeling. The mechanism(s) by which inflammatory cells persist in VZV-infected arteries is unknown; however, virus-induced dysregulation of programmed death ligand 1 (PD-L1) may play a role. Specifically, PD-L1 is expressed on virtually all nucleated cells and suppresses the immune system by interacting with the programmed cell death protein receptor 1 found exclusively on immune cells; thus, downregulation of PD-L1 may promote inflammation as seen in some autoimmune diseases...
September 14, 2016: Journal of Virology
Ana Lucía Rodríguez-Perea, Johanna Gutierrez-Vargas, Gloria Patricia Cardona-Gómez, Carlos Julio Montoya Guarin, Mauricio Rojas, Paula Andrea Velilla Hernández
Regulatory T cells (Tregs) inhibit the activation of the immune response which could down-regulate the systemic and focal activation observed during ischemic stroke. In fact, in animal models, Tregs infiltrate the infarcted brain and reduce the pro-inflammatory cytokine production and infarct volume, mainly in late stages of ischemia. Recently, an expansion and greater suppressive capacity of circulating Tregs after treatment with statins was observed, in addition to their cardio- and neuroprotective actions demonstrated previously...
September 10, 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
Weiying Xie, Lili Fang, Shuyuan Gan, Haojun Xuan
Stroke causes brain injury with neuroinflammation which exacerbates the neuronal damage. Recent studies show that anti-inflammatory cytokine interleukin-19 (IL-19) plays a critical part in the inflammatory and ischemic vascular diseases, yet its potential role in ischemic stroke is unknown. Here, we tested the hypothesis that IL-19 exerts protective effects against brain ischemia by modulating inflammation after stroke. Mice were injected intraperitoneally with 10ng/g per day recombinant mouse IL-19 starting pre-stroke, and were subjected to transient middle cerebral artery occlusion...
November 1, 2016: Brain Research
Somayyeh Hamzei Taj, Widuri Kho, Markus Aswendt, Franziska M Collmann, Claudia Green, Joanna Adamczak, Annette Tennstaedt, Mathias Hoehn
Mononuclear phagocytes respond to ischemic stroke dynamically, undergoing an early anti-inflammatory and protective phenotype followed by the pro-inflammatory and detrimental type. These dual roles of microglia/macrophages suggest the need of subtle adjustment of their polarization state instead of broad suppression. The most abundant brain-specific miRNA, miR-124, promotes neuronal differentiation but can also modulate microglia activation and keeps them in a quiescent state. We addressed whether the intracerebral injection of miR-124 in a mouse model of ischemic stroke before or after the peak phase of the pro-inflammatory polarization modifies the pro-/anti- inflammatory balance...
August 18, 2016: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
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 neuroinflammtory response, resolution of inflammation, and transition to neurological recovery and regeneration...
August 15, 2016: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
Sanjay S Gautam, Ronan F O'Toole
Chronic obstructive pulmonary disease (COPD) is one of the main causes of human mortalities globally after heart disease and stroke. There is increasing evidence of an aetiological association between COPD and pneumonia, the leading infectious cause of death globally in children under 5 years. In this review, we discuss the known risk factors of COPD that are also shared with pneumonia including smoking, air pollution, age and immune suppression. We review how lung pathology linked to a previous history of pneumonia may heighten susceptibility to the development of COPD in later life...
June 16, 2016: COPD
Lei Zhang, Yanxia Huang, Yinyao Lin, Yilong Shan, Sha Tan, Wei Cai, Haiyan Li, Bingjun Zhang, Xuejiao Men, Zhengqi Lu
BACKGROUND: Cholera toxin B subunit (CTB) has multifaceted immunoregulatory functions. Immunity plays an important role in the mechanism of stroke. However, little is known about whether CTB is beneficial for stroke. METHODS: CTB was administered intraperitoneally after ischemia to rats subjected to transient focal ischemia. Infarct volumes, body weight loss, and neurologic deficits were measured. Cytokines, microglia/macrophage activation, and transcriptional factors in the ischemic brain were tested...
2016: Journal of Neuroinflammation
Christopher Garst, Makenzie Fulmer, Doug Thewke, Stacy Brown
Atherosclerosis is a disease characterized by plaque formation due to an accumulation of fat, cholesterol, and immune cells in the walls of arteries. If a plaque ruptures, an occlusive thrombosis may form that causes either a heart attack or stroke. Macrophages express CB-2 receptors, and are one type of immune cell that plays a role in plaque destabilization and rupture. Endocannabinoids anandamide (AEA) and 2-arachidonyl glycerol (2-AG) have been found to have activity on CB-1 and CB-2 receptors throughout the body and immune system...
May 2016: European Journal of Lipid Science and Technology: EJLST
Lei Zuo, Luhang Shi, Fuling Yan
BACKGROUND: Sympathetic nervous system(SNS) is involved in the mechanism of immune suppression after stroke. Furthermore, as the pro-inflammatory effect of nuclear factor kappa B(NF-kB) is inhibited after stroke, which is regulated by cyclic adenosine monophosphate(cAMP) and proteinkinase A(PKA). The cAMP-PKA-NF-kB pathway might play an important role in noradrenergic-mediated immune dysfunction. AIM: The purpose of our research is to analyze how SNS interfere with the immune system after acute stroke and the underlying mechanism of cAMP-PKA-NF-kB pathway in regulating the inflammation...
August 3, 2016: Neuroscience Letters
Johanna Ruhnau, Juliane Schulze, Bettina von Sarnowski, Marie Heinrich, Sönke Langner, Christian Pötschke, Anika Wilden, Christof Kessler, Barbara M Bröker, Antje Vogelgesang, Alexander Dressel
BACKGROUND AND PURPOSE: Regulatory T cells (Tregs) have been suggested to modulate stroke-induced immune responses. However, analyses of Tregs in patients and in experimental stroke have yielded contradictory findings. We performed the current study to assess the regulation and function of Tregs in peripheral blood of stroke patients. Age dependent expression of CD39 on Tregs was quantified in mice and men. METHODS: Total FoxP3(+) Tregs and CD39(+)FoxP3(+) Tregs were quantified by flow cytometry in controls and stroke patients on admission and on days 1, 3, 5, and 7 thereafter...
2016: Mediators of Inflammation
Corinne Benakis, David Brea, Silvia Caballero, Giuseppe Faraco, Jamie Moore, Michelle Murphy, Giulia Sita, Gianfranco Racchumi, Lilan Ling, Eric G Pamer, Costantino Iadecola, Josef Anrather
Commensal gut bacteria impact the host immune system and can influence disease processes in several organs, including the brain. However, it remains unclear whether the microbiota has an impact on the outcome of acute brain injury. Here we show that antibiotic-induced alterations in the intestinal flora reduce ischemic brain injury in mice, an effect transmissible by fecal transplants. Intestinal dysbiosis alters immune homeostasis in the small intestine, leading to an increase in regulatory T cells and a reduction in interleukin (IL)-17-positive γδ T cells through altered dendritic cell activity...
May 2016: Nature Medicine
Laura L Hocum Stone, Feng Xiao, Jessica Rotschafer, Zhenhong Nan, Mario Juliano, Cyndy D Sanberg, Paul R Sanberg, Nicole Kuzmin-Nichols, Andrew Grande, Maxim C-J Cheeran, Walter C Low
Despite the high prevalence and devastating outcome, there remain a few options for treatment of ischemic stroke. Currently available treatments are limited by a short time window for treatment and marginal efficacy when used. We have tested a human umbilical cord blood-derived stem cell line that has been shown to result in a significant reduction in stroke infarct volume as well as improved functional recovery following stroke in the rat. In the present study we address the mechanism of action and compared the therapeutic efficacy of high- versus low-passage nonhematopoietic umbilical cord blood stem cells (nh-UCBSCs)...
2016: Cell Transplantation
Min Jung Lee, Minhee Jang, Chun-Sik Bae, Kyoung-Sun Park, Hak-Jae Kim, Sanghyun Lee, Sang Won Lee, Young Ock Kim, Ik-Hyun Cho
A traditional herbal prescription, Kyung-Ok-Ko (KOK), composed of Rehmannia glutinosa Liboschitz var. purpurae, Lycium chinense, Aquillaria agallocha, Poria cocos, Panax ginseng, and honey, has been widely used in Oriental medicine as an invigorant or age-related diseases such as amnesia and stroke. However, the beneficial value of KOK on uterine dysfunction related to hyperandrogenism is largely unknown. We investigated the effect of KOK (2.0 g/kg/day, per os) on endometrial abnormalities in a dehydroepiandrosterone (DHEA, subcutaneous)-induced polycystic ovarian syndrome (PCOS) rat model...
February 22, 2016: Rejuvenation Research
Ryan Mattie, Zack McCormick, Henry Huie
Toxoplasma gondii is an opportunistic infection that often presents in the setting of acquired immunodeficiency syndrome. The infection can cause severe and potentially fatal encephalitis because of the reactivation of latent infections in the setting of immune suppression. Diagnosing toxoplasmosis encephalitis (TE) in immunocompromised patients often is difficult because the signs and symptoms can be nonspecific, but making a diagnosis of TE is even more challenging in a patient who is not known to have human immunodeficiency virus/acquired immunodeficiency syndrome and shows no other signs of being immunocompromised...
June 2016: PM & R: the Journal of Injury, Function, and Rehabilitation
Silke Neumann, Nicholas J Shields, Thomas Balle, Mary Chebib, Andrew N Clarkson
Stroke is one of the leading causes of death and long-term disability, with limited treatment options available. Inflammation contributes to damage tissue in the central nervous system across a broad range of neuropathologies, including Alzheimer's disease, pain, Schizophrenia, and stroke. While the immune system plays an important role in contributing to brain damage produced by ischemia, the damaged brain, in turn, can exert a powerful immune-suppressive effect that promotes infections and threatens the survival of stroke patients...
2015: International Journal of Molecular Sciences
Chun-Yang Zhao, Hui Lei, Yu Zhang, Lin Li, Shao-Feng Xu, Jie Cai, Ping-Ping Li, Ling Wang, Xiao-Liang Wang, Ying Peng
Microglia activation-induced neuroinflammation contributes to neuronal damage in neurodegenerative diseases. Inhibition of microglia activation and reduction of major neurotoxic cytokines have been becoming a therapeutic strategy for neurodegenerative diseases. L-3-n-Butylphthalide (L-NBP) has shown the potent neuroprotective effects in stroke and Alzheimer's disease animal models. The present study investigated the immune modulatory effects of L-NBP on pro-inflammatory cytokines and microglia activation in brain tissue induced by systemic lipopolysaccharide (LPS) treatment in C57BL/6 mice...
2016: Journal of Asian Natural Products Research
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