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ischemic stroke inflammation

Megan A Evans, Brad R S Broughton, Grant R Drummond, Henry Ma, Thanh G Phan, Euan M Wallace, Rebecca Lim, Christopher G Sobey
Stroke is a leading cause of death and disability and new therapies are desperately needed. Given the complex nature of ischemic brain injury, it has been postulated that cell-based therapies may be useful. However, cell resources, invasive extraction procedures, immunological rejection, tumorigenesis and ethical challenges make it unlikely that many stem cell types could serve as a practical source for therapy. By contrast, these issues do not pertain to human amnion epithelial cells (hAECs), which are placenta-derived stem cells...
August 2018: Neural Regeneration Research
Laura Ramiro, Alba Simats, Teresa García-Berrocoso, Joan Montaner
Stroke is the fifth leading cause of death and the most frequent cause of disability worldwide. Currently, stroke diagnosis is based on neuroimaging; therefore, the lack of a rapid tool to diagnose stroke is still a major concern. In addition, therapeutic approaches to combat ischemic stroke are still scarce, since the only approved therapies are directed toward restoring blood flow to the affected brain area. However, due to the reduced time window during which these therapies are effective, few patients benefit from them; therefore, alternative treatments are urgently needed to reduce stroke brain damage in order to improve patients' outcome...
2018: Therapeutic Advances in Neurological Disorders
Antoine Drieu, Damien Levard, Denis Vivien, Marina Rubio
So far, intravenous tissue-type plasminogen activator (tPA) and mechanical removal of arterial blood clot (thrombectomy) are the only available treatments for acute ischemic stroke. However, the short therapeutic window and the lack of specialized stroke unit care make the overall availability of both treatments limited. Additional agents to combine with tPA administration or thrombectomy to enhance efficacy and improve outcomes associated with stroke are needed. Stroke-induced inflammatory processes are a response to the tissue damage due to the absence of blood supply but have been proposed also as key contributors to all the stages of the ischemic stroke pathophysiology...
2018: Therapeutic Advances in Neurological Disorders
Mark T Mackay, Maja Steinlin
This review will discuss important developments in childhood arterial ischemic stroke over the past decade, focusing on improved understanding of the causes, consequences, and targets for intervention. Risk factors for childhood arterial ischemic stroke are different to adults. Infections, particularly herpes group viruses, are important precipitants for stroke. Non-atherosclerotic arteriopathies are the most common cause of childhood arterial ischemic stroke and an important predictor of recurrent events. Recent advances include the identification of serum biomarkers for inflammation and endothelial injury, and imaging biomarkers to monitor for vascular progression...
August 6, 2018: International Journal of Stroke: Official Journal of the International Stroke Society
Grant M Liska, Trenton Lippert, Eleonora Russo, Norton Nieves, Cesar V Borlongan
Stroke continues to be an extremely prevalent disease and poses a great challenge in developing safe and effective therapeutic options. Hyperbaric oxygen therapy (HBOT) has demonstrated significant pre-clinical effectiveness for the treatment of acute ischemic stroke, and limited potential in treating chronic neurological deficits. Reported benefits include reductions in oxidative stress, inflammation, neural apoptosis, and improved physiological metrics such as edema and oxygen perfusion, all of which contribute to improved functional recovery...
June 2018: Conditioning medicine
Wei Li, Jin Liu, Jie-Ru Chen, Yong-Ming Zhu, Xue Gao, Yong Ni, Bo Lin, Huanqiu Li, Shi-Gang Qiao, Chen Wang, Hui-Ling Zhang, Gui-Zhen Ao
Receptor-interacting protein 1 kinase (RIP1K) plays a key role in necroptosis. Necrostatin-1 (Nec-1), a specific inhibitor of RIP1K, provides neuroprotection against ischemic brain injury, associating with inhibition of inflammation. Recently, our group synthesized a novel analogue of Nec-1, 5-(3',5'-dimethoxybenzal)-2-thio-imidazole-4-ketone (DTIO). The present study investigated the effect of DTIO on ischemic stroke-induced brain injury in both acute and chronic phase and its underlying mechanism. In vivo, DTIO treatment reduced infarct volume and improved neurological deficits in the acute phase after permanent middlecerebralartery occlusion (pMCAO) and it also attenuated brain atrophy and promoted brain functional recovery in the chronic phase post-cerebralischemia/reperfusion (I/R)...
August 1, 2018: Neuroscience
Romain Chopard, Gregory Piazza, Seth Alan Gale, Umberto Campia, Ida Ehlers Albertsen, Jisoo Kim, Samuel Z Goldhaber
Atrial fibrillation increases the risk of stroke by a factor of 4- to 5-fold, and dementia is a common consequence of stroke. However, atrial fibrillation has been associated with cognitive impairment and dementia, even in patients without prior overt stroke. Non-ischemic mechanisms include cerebral hypoperfusion, vascular inflammation, brain atrophy, genetic factors, and shared risk factors such as age or hypertension. Critical appraisal of studies evaluating the association between atrial fibrillation and dementia in stroke-free patients reveals that several suffer from methodological issues, such as not including silent stroke or anticoagulation therapy in multivariate analyses...
August 1, 2018: American Journal of Medicine
Sara Nikseresht, Fariba Khodagholi, Abolhassan Ahmadiani
Necroptosis, a novel type of programmed cell death, is involved in ischemia-reperfusion-induced brain injury. Sirtuin 1 (Sirt1), as a well-known member of histone deacetylase class III, plays pivotal roles in inflammation, metabolism, and neuron loss in cerebral ischemia. We explored the relationship between Sirt1 and the necroptosis signaling pathway and its downstream events by administration of ex-527, as a selective and potent inhibitor of Sirt1, and necrostatin-1 (nec-1), as a necroptosis inhibitor, in an animal model of focal cerebral ischemia...
August 1, 2018: Journal of Cellular Physiology
Lili Lin, Da Sun, Jing Chang, Ming Ma, Xiaoying Zhou, Min Zhao, Jian Li
Cocaine and amphetamine‑regulated transcript (CART) is a neuropeptide that can protect brains against ischemic injury. The aim of the present study was to investigate the effects of the CART within ischemic stroke and it possible mechanism. The expression levels of dopamine (DA) and CART in ischemic brain tissues of mice were measured following middle cerebral artery occlusion (MCAO). After receiving the treatment of DA and CART, the infarct volume of brain was measured in mice with MCAO. In addition, the function and potential mechanism of CART in ischemic stroke were further investigated...
July 19, 2018: Molecular Medicine Reports
Jie Chen, Zengrui Zhang, Luyun Chen, Xiaowen Feng, Wangwang Hu, Wanqian Ge, Xianmei Li, Pingping Jin, Bei Shao
OBJECTIVE: Leukocytes play a crucial role in inflammation and immune response. This study aims to demonstrate the value of changes in leukocytes levels 24 hours after intravenous thrombolysis to predict prognosis in acute ischemic stroke (AIS). METHODS: From Jan 2016 to Oct 2017, the patients who suffered AIS to our center within 4.5 hours of symptom onset were all treated with recombinant tissue-type plasminogen activator. Data from 213 AIS patients were analyzed...
July 29, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
S Loppi, N Kolosowska, O Kärkkäinen, P Korhonen, M Huuskonen, A Grubman, H Dhungana, S Wojciechowski, Y Pomeshchik, M Giordano, H Kagechika, A White, S Auriola, J Koistinaho, G Landreth, K Hanhineva, K Kanninen, T Malm
Ischemic stroke is amongst the leading causes of death and disabilities. The available treatments are suitable for only a fraction of patients and thus novel therapies are urgently needed. Blockage of one of the cerebral arteries leads to massive and persisting inflammatory reaction contributing to the nearby neuronal damage. Targeting the detrimental pathways of neuroinflammation has been suggested to be beneficial in conditions of ischemic stroke. Nuclear receptor 4A -family (NR4A) member Nurr1 has been shown to be a potent modulator of harmful inflammatory reactions, yet the role of Nurr1 in cerebral stroke remains unknown...
July 28, 2018: Brain, Behavior, and Immunity
Mathilde Chevin, Clémence Guiraut, Guillaume Sébire
BACKGROUND: Hypothermia is increasingly tested in several neurological conditions, such as neonatal encephalopathy, stroke, traumatic brain injury, subarachnoid hemorrhage, spinal cord injury, and neurological outcomes of cardiac arrest. Current studies aim to increase benefits of hypothermia with new add-on therapies including immunomodulatory agents. Hypothermia has been shown to affect the metabolism of commonly used drugs, including those acting on neuroimmune pathways. OBJECTIVE: This study focuses on the effect of hypothermia on interleukin-1 receptor antagonist pharmacodynamics in a model of neonatal encephalopathy...
July 30, 2018: Journal of Neuroinflammation
Mohammad-Reza Rahmani, Ali Shamsizadeh, Elham Hakimizadeh, Mohammad Allahtavakoli
Administration of tissue plasminogen activator (tPA) during first 3-4.5 h after ischemic stroke is the main therapeutic strategy; however, its using after that, leads to reperfusion injury and neurotoxic effects. Additionally, inflammation has a critical role in secondary injury after late reperfusion therapy. Thus, this project was designed to explore the effects of JZL-184 (JZL), an agonist of type 1 cannabinoid receptor (CB1), on the side effects of recombinant tPA (r-tPA), which is administrated after 5 h of stroke onset in the mice middle cerebral artery occlusion (MCAO) model...
July 25, 2018: Inflammation
Xiaojun Fei, Xu Zhang, Qi Wang, Jingbo Li, Hao Shen, Xuanye Wang, Hongquan Liu, Weiwei Tao
Ischemic stroke is an increasingly important public health problem, and no effective treatments are approved. Xijiao Dihuang Decoction (XDD), a famous herbal formula for treating hemorrhagic fever syndromes, has been shown to exert powerful neuroprotective property. The aim of this study was to identify the chemical constituents in XDD, observe the neuroprotective effect of XDD against acute ischemic stroke, and explore the specific mechanisms by which these effects were mediated. With UHPLC-Q/TOF-MS, 47 components in XDD were detected and 25 of them were identified...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
Shanshan Song, Shaoxia Wang, Victoria M Pigott, Tong Jiang, Lesley M Foley, Abhishek Mishra, Rachana Nayak, Wen Zhu, Gulnaz Begum, Yejie Shi, Karen E Carney, T Kevin Hitchens, Gary E Shull, Dandan Sun
Na+ /H+ exchanger (NHE1) activation is required for multiple microglial functions. We investigated effects of selective deletion of microglial Nhe1 in Cx3cr1-CreER ;Nhe1f/f mice on neuroinflammation and tissue repair after ischemic stroke. Infarct volume was similar in corn oil or tamoxifen (Tam)-treated mice at 48 hr and 14 days post-stroke. However, the Tam-treated mice showed significantly higher survival rate and faster neurological function recovery during day 1-14 post-stroke. Deletion of microglial Nhe1 prevented the elevation of CD11b+ /CD45low-med microglia in the ischemic hemisphere at day 3 post-stroke, but stimulated expression of Ym1, CD68, TGF-β, IL-10, decreased expression of CD86 and IL-1β, and reduced GFAP+ reactive astrocytes...
July 25, 2018: Glia
Wen-Hung Chen, Hsu-Ling Yeh, Chiung-Wen Tsao, Li-Ming Lien, Arthur Chiwaya, Javad Alizargar, Chyi-Huey Bai
Translocator protein 18 kDa (TSPO) has been used as a biomarker of brain injury and inflammation in various neurological diseases. In this study, we measured the level of TSPO in acute ischemic stroke patients and determined its association with the degree of stroke severity and its ability to predict stroke functional outcomes. In total, 38 patients with moderate to severe acute ischemic stroke were enrolled. Demographic information, cerebral risk factors, and stroke severity were examined at the baseline...
2018: Disease Markers
Shan Lu, Hang Li, Kai Li, Xiao-Di Fan
Ischemic stroke is an acute cerebrovascular disease due to poor blood flow to the brain. Nevertheless, there is still no effective therapy for it and the pathology contributing to ischemic stroke is not fully understood. Histone Deacetylase 9 (HDAC9) is a class IIa chromatin-modifying enzyme. HDAC9 gene region is a leading risk locus for large artery atherosclerotic stroke. However, the mechanisms linking HDAC9 to ischemic remain elusive. In the study, we attempted to explore HDAC9-associated inflammatory response using the wild type (WT) and HDAC9-knockout (KO) mice with brain ischemic injury...
July 18, 2018: Biochemical and Biophysical Research Communications
Ulises Gómez-Pinedo, Leyre Sanchez-Rojas, María Soledad Benito-Martin, Cristina Lendinez, Gonzalo León-Espinosa, Fernando Rascón, Jone Herrero, Begoña Castro, Lidia Moreno-Jiménez, Maite Del Olmo, Jordi A Matias-Guiu, Jorge Matias-Guiu, Juan A Barcia
INTRODUCTION: Stroke represents an attractive target for cell therapy. Although different types of cells have been employed in animal models with variable results, the human adipose-derived stem cells (hASCs) have demonstrated favorable characteristics in the treatment of diseases with inflammatory substrate, but experience in their intracerebral administration is lacking. The purpose of this study is to evaluate the effect and safety of the intracerebral application of hASCs in a stroke model...
July 18, 2018: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
Lisa Rancan, Sergio D Paredes, Cruz García, Pablo González, Cruz Rodríguez-Bobada, Mario Calvo-Soto, Bryan Hyacinthe, Elena Vara, Jesús A F Tresguerres
Aging is associated with an increase in stroke risk. Melatonin, a potent free radical scavenger and broad spectrum antioxidant, has been shown to counteract inflammation and apoptosis in brain injury. However, little is known on the possible protective effects of melatonin in aged individuals affected by brain ischemia. Also, using melatonin before or after an ischemic stroke may result in significantly different molecular outcomes. The objective of the present study was to compare the effects of pre-ischemia vs...
July 19, 2018: International Journal of Molecular Sciences
Yijun Cheng, Jieyu Zan, Yaying Song, Guoyuan Yang, Hanbing Shang, Weiguo Zhao
Intestinal injury is a common complication following intracerebral hemorrhage (ICH), which leads to malnutrition, impaired immunity and unsatisfactory prognosis. Previous studies have revealed the pathogenesis of intestinal injury following traumatic brain injury using ischemic stroke models. However, the effects of ICH on intestinal injury remain unknown. The present study aimed to investigate the pathological alterations and molecular mechanism, as well as the time course of intestinal injury following ICH in mice...
October 2018: International Journal of Molecular Medicine
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