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Stroke inflammation

Xiaodi Chen, Jiyong Zhang, Boram Kim, Siddhant Jaitpal, Steven S Meng, Kwame Adjepong, Sayumi Imamura, Hidenori Wake, Masahiro Nishibori, Edward G Stopa, Barbara S Stonestreet
Inflammation contributes to neonatal brain injury. Pro-inflammatory cytokines represent key inflammatory meditators in neonatal hypoxic-ischemic (HI) brain injury. The high mobility group box-1 (HMGB1) protein is a nuclear protein with pro-inflammatory cytokine properties when it is translocated from the nucleus and released extracellularly after stroke in adult rodents. We have previously shown that HMGB1 is translocated from the nucleus to cytosolic compartment after ischemic brain injury in fetal sheep. In the current study, we utilized the Rice-Vannucci model to investigate the time course of HMGB1 translocation and release after HI injury in neonatal rats...
September 11, 2018: Experimental Neurology
Emőke Horváth, Adina Huțanu, Liviu Chiriac, Minodora Dobreanu, Alex Orădan, Előd-Ernő Nagy
Clinical and experimental observations emphasize that inflammation is a direct risk factor for stroke. We performed a detailed histological and immunohistochemical analysis, assisted by digital morphometry, to compare the representative brain lesions in the ischemic core and penumbra in a rat model. Focal neuronal necrosis and degeneration were significantly more intense in the core, whereas inflammatory infiltration, MPO, CD68, CD3, FXIII, Cox-2, iNOS2, Arg-1 expressions were stronger in the penumbra. Our findings indicate that neuroinflammation affects the penumbra more than the core and suggest that targeted modulation of the cellular infiltrate could be exploited to save brain volume...
August 9, 2018: Journal of Neuroimmunology
Kavitha Kothur, Christopher Troedson, Richard Webster, Sushil Bandodkar, Stephanie Chu, Louise Wienholt, Alun Pope, Mark T Mackay, Russell C Dale
Aim To determine the role of inflammation in pediatric transient focal cerebral arteriopathy using cerebrospinal fluid cytokine/chemokines as biomarkers. Methods We measured 32 cytokine/chemokines in acute cerebrospinal fluid collected from children with stroke due to focal cerebral arteriopathy (n = 5) using multiplex immunoassay and compared with two patients with arterial ischemic stroke due to other causes (non-focal cerebral arteriopathy group, vertebral dissection, n = 1; cryptogenic, n = 1), pediatric encephalitis (n = 43), and non-inflammatory neurological disease controls (n = 20)...
September 13, 2018: International Journal of Stroke: Official Journal of the International Stroke Society
Zaal Kokaia, Vladimer Darsalia
Ischemic stroke is the second most common cause of death worldwide and a major cause of disability. It takes place when the brain does not receive sufficient blood supply due to the blood clot in the vessels or narrowing of vessels' inner space due to accumulation of fat products. Apart from thrombolysis (dissolving of blood clot) and thrombectomy (surgical removal of blood clot or widening of vessel inner area) during the first hours after an ischemic stroke, no effective treatment to improve functional recovery exists in the post-ischemic phase...
2018: Results and Problems in Cell Differentiation
Raphaël Duivenvoorden, Max L Senders, Mandy M T van Leent, Carlos Pérez-Medina, Matthias Nahrendorf, Zahi A Fayad, Willem J M Mulder
Atherosclerosis is a chronic disease of the large arteries and the underlying cause of myocardial infarction and stroke. Atherosclerosis is driven by cholesterol accumulation and subsequent inflammation in the vessel wall. Despite the clinical successes of lipid-lowering treatments, atherosclerosis remains one of the major threats to human health worldwide. Over the past 20 years, insights into cardiovascular immunopathology have provided a plethora of new potential therapeutic targets to reduce the risk of atherosclerosis and have shifted the therapeutic focus from lipids to inflammation...
September 12, 2018: Nature Reviews. Cardiology
Zhaoshi Zheng, Songyan Liu, Chunhui Wang, Xuemei Han
Long noncoding RNAs (lncRNAs) play crucial roles in the regulation of pathological process of ischemic stroke (IS) via affecting cell apoptosis, inflammation, cell death, and angiogenesis. LncRNA growth arrest-specific 5 (GAS5) was observed to be up-regulated in IS, acting as a competing endogenous RNA for miR-137 to mediate the Notch1 signaling pathway. In this study, we aimed to whether an insertion/deletion polymorphism (rs145204276) in the promoter of GAS5 was related to the risk of IS. The rs145204276 was genotyped using polymerase chain reaction (PCR)-polyacrylamide gel electrophoresis in 509 patients with IS and 668 healthy controls with frequencies matched to cases regarding age, gender, living area, and ethnicity...
September 6, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Isabella Wimmer, Tobias Zrzavy, Hans Lassmann
Neuroinflammation has been suggested as an attractive treatment target in stroke, since it offers a broader therapeutic window in comparison to currently established thrombolytic approaches. Inflammatory cells of both the innate and the adaptive immune system have been identified in experimental as well as human stroke lesions. In animal models, various therapeutic strategies targeting neuroinflammation have shown beneficial effects, however, translation to human disease has so far been disappointing. Comparisons of the numerous experimental findings with until now rather limited human data reveal that despite similarities in the core signature of the inflammatory reaction, human stroke lacks clearly definable temporal and spatial sequences of lesion maturation that can be generalized and applied for a large patient population...
October 15, 2018: Journal of Neuroimmunology
Seyed Esmaeil Khoshnam, Alireza Sarkaki, Masome Rashno, Yaghoob Farbood
Ischemic stroke is one of the leading causes of neurological deterioration and mortality worldwide. Neuroprotective strategies are being investigated to minimize cognitive deficits after ischemic events. Here we investigated the neuroprotective potential of vanillic acid (VA) in an animal model of transient bilateral common carotid artery occlusion and reperfusion (BCCAO/R). Adult male Wistar rats (250-300 g) were randomly divided in 4 groups and submitted to either cerebral hypoperfusion-reperfusion or a sham surgery after two-weeks of pretreatment with VA and/or normal saline...
September 6, 2018: Life Sciences
Luting Poh, Sung-Wook Kang, Sang-Ha Baik, Gavin Yong Quan Ng, David T She, Priyanka Balaganapathy, S Thameem Dheen, Tim Magnus, Mathias Gelderblom, Christopher G Sobey, Edward H Koo, David Y Fann, Thiruma V Arumugam
Stroke is the second leading cause of death in the world and a major cause of long-term disability. Recent evidence has provided insight into a newly described inflammatory mechanism that contributes to neuronal and glial cell death, and impaired neurological outcome following ischemic stroke - a form of sterile inflammation involving innate immune complexes termed inflammasomes. It has been established that inflammasome activation following ischemic stroke contributes to neuronal cell death, but little is known about inflammasome function and cell death in activated microglial cells following cerebral ischemia...
September 5, 2018: Brain, Behavior, and Immunity
Jacek M Kwiecien
As the systematic work on the pathogenesis of the white matter injury in the spinal cord models progresses, it becomes obvious that a severe and extraordinarily protracted, destructive inflammation follows the initial injury. Appropriate anti-inflammatory therapies of sufficient duration should not only inhibit but also lead to the elimination of this destructive inflammation, thus resulting in neuroprotection of the spinal cord tissue and a greater preservation of the neurologic function. While dexamethasone, a powerful, anti-inflammatory steroid analog administered continuously by subdural infusion for 7 days inhibited severe macrophage infiltration in the cavity of injury, the dose used was remarkably toxic...
2018: Methods in Molecular Biology
Chunhua Shi, Annegret Ulke-Lemée, Jingti Deng, Zarah Batulan, Edward R O'Brien
Previously, we reported that elevated serum levels of heat shock protein 27 (HSP27) are predictive of a lower risk of having a heart attack, stroke, or death from cardiovascular disease. Moreover, augmenting HSP27 (or the murine ortholog, HSP25) attenuated experimental atherogenesis, reduced inflammation, and lowered cholesterol levels. Recently, we noted that HSP27 activates NF-κB via TLR-4, resulting in attenuation of plaque inflammation; however, the precise anti-atherosclerosis mechanisms mediated by extracellular HSP27 are incompletely understood...
September 6, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Fangbin Chen, Zhiyang Liu, Wei Peng, Zhiqin Gao, Hui Ouyang, Tongjun Yan, Songbai Ding, Zhankui Cai, Bin Zhao, Longjin Mao, Zhiyong Cao
Vascular dementia (VD) is a syndrome characterized by progressive cognitive decline. According to previous studies, stroke is considered to be a risk factor for VD. The disruption of the blood-brain barrier (BBB) is pivotal to the pathology of stroke, as it contributes to post-stroke inflammation and edema. It has been reported that the Eph/Ephrin signaling pathway serves an important role in central nervous system injury. However, the role of EphrinA1/EphA4 signaling in BBB damage following ischemic stroke has not yet been reported...
September 2018: Experimental and Therapeutic Medicine
Xiaowen Yu, Xiaoqing Wang, Shuxiong Zeng, Xiping Tuo
Strokes are a major cause of neurological disability. Stem cell replacement therapy is a potential novel strategy of treating patients that have experienced strokes. The present study examined the protective role of neural stem cell (NSC) administration in oxygen-glucose deprivation (OGD) injury and ischemic stroke animal models. Primary cultured embryonic NSCs and brain microvascular endothelial cells were indirectly co-cultured for in vitro testing. A rat model of embolic middle cerebral artery occlusion (MCAO) was used to assess the morphological and functional changes that occur following treatment with NSCs...
September 2018: Experimental and Therapeutic Medicine
Kevin C Maki, Fulya Eren, Martha E Cassens, Mary R Dicklin, Michael H Davidson
The 2015 Dietary Guidelines for Americans recommend limiting the intake of saturated fatty acids (SFAs) to <10% of energy/d and replacing dietary SFAs with unsaturated fatty acids. A Presidential Advisory from the American Heart Association recently released its evaluation of the relation between dietary fats and cardiovascular disease (CVD), and also recommended a shift from SFAs to unsaturated fatty acids, especially polyunsaturated fatty acids (PUFAs), in conjunction with a healthy dietary pattern. However, the suggestion to increase the intake of PUFAs in general, and omega-6 (n-6) PUFAs in particular, continues to be controversial...
September 4, 2018: Advances in Nutrition
Christoph J Griessenauer, Sean Farrell, Atom Sarkar, Ramin Zand, Vida Abedi, Neil Holland, Andrew Michael, Christopher L Cummings, Raghu Metpally, David J Carey, Oded Goren, Neil Martin, Philipp Hendrix, Clemens M Schirmer
Investigation of genetic susceptibility to cerebrovascular disease has been of growing interest. A systematic review of human studies assessing neurogenomic aspects of cerebrovascular disease was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Any association study exploring genetic variants located in the exome associated with one of the major cerebrovascular diseases with at least 500 subjects was eligible for inclusion. Of 6874 manuscripts identified, 35 studies met the inclusion criteria...
September 5, 2018: Journal of Cerebral Blood Flow and Metabolism
Gaby Enzmann, Soghra Kargaran, Britta Engelhardt
Reperfusion injury following ischemic stroke is a complex pathophysiological process involving numerous mechanisms ranging from the release of excitatory amino acids and ion disequilibrium to the induction of apoptosis and necrosis, to oxidative stress and inflammation. The migration of neutrophils into the brain parenchyma and release of their abundant proteases are generally considered the main cause of neuronal cell death and acute reperfusion injury following ischemic stroke. Recent findings in experimental and human stroke have challenged this view, as the majority of neutrophils were rather found to accumulate within the neurovascular unit (NVU) and the subarachnoid space (SAS) where they remain separated from the brain parenchyma by the glia limitans ...
2018: Therapeutic Advances in Neurological Disorders
Jason E Hawkes, Bernice Y Yan, Tom C Chan, James G Krueger
Psoriasis vulgaris is a common, heterogeneous, chronic inflammatory skin disease characterized by thickened, red, scaly plaques and systemic inflammation. Psoriasis is also associated with multiple comorbid conditions, such as joint destruction, cardiovascular disease, stroke, hypertension, metabolic syndrome, and chronic kidney disease. The discovery of IL-17-producing T cells in a mouse model of autoimmunity transformed our understanding of inflammation driven by T lymphocytes and associations with human inflammatory diseases, such as psoriasis...
September 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Leticia Gonzalez, Ulises Novoa, Jackeline Moya, Luigi Gabrielli, Jorge E Jalil, Lorena García, Mario Chiong, Sergio Lavandero, María Paz Ocaranza
Hypertension-induced cardiovascular and renal damage can be mediated by activation of the renin-angiotensin-aldosterone system. There are different factors beyond renin-angiotensin-aldosterone system involved in hypertension and renal damage. Inflammation has emerged as an important mediator of hypertension and cardiovascular and kidney damage. Angiotensin-(1-9), a peptide of the renin-angiotensin system, counter-regulates both the physiological and pathological actions of angiotensin II. Recent data has shown that angiotensin-(1-9) protects the heart and blood vessels from adverse cardiovascular remodeling in experimental models of hypertension and/or heart failure and reduces cardiac fibrosis in stroke-prone, spontaneously hypertensive rats...
September 1, 2018: Biochemical Pharmacology
Milla Pietiäinen, John M Liljestrand, Elisa Kopra, Pirkko J Pussinen
Clinical periodontitis is associated with an increased risk for cardiovascular diseases (CVDs) through systemic inflammation as the etiopathogenic link. Whether the oral microbiota, especially its quality, quantity, serology, and virulence factors, plays a role in atherogenesis is not clarified. Patients with periodontitis are exposed to bacteria and their products, which have access to the circulation directly through inflamed oral tissues and indirectly (via saliva) through the gastrointestinal tract, resulting in systemic inflammatory and immunologic responses...
October 2018: European Journal of Oral Sciences
Genevieve Eastabrook, Tuba Aksoy, Samantha Bedell, Debbie Penava, Barbra de Vrijer
Preeclampsia is a serious pregnancy condition defined as new-onset hypertension and proteinuria, commonly characterized as either early, 'placental', or late onset, 'maternal', using a cut-off of 34 weeks gestation. However, it may be more useful to differentiate between the vascular remodelling and placental invasion vs. inflammation and metabolic pathophysiology that underlie these forms of preeclampsia. Due to rising rates of obesity, the late-onset, maternal form is increasingly occurring earlier in pregnancy...
July 2018: Pregnancy Hypertension
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