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https://www.readbyqxmd.com/read/28912641/toll-like-receptor-2-a-novel-therapeutic-target-for-ischemic-white-matter-injury-and-oligodendrocyte-death
#1
REVIEW
Jun Young Choi, Byung Gon Kim
Despite paramount clinical significance of white matter stroke, there is a paucity of researches on the pathomechanism of ischemic white matter damage and accompanying oligodendrocyte (OL) death. Therefore, a large gap exists between clinical needs and laboratory researches in this disease entity. Recent works have started to elucidate cellular and molecular basis of white matter injury under ischemic stress. In this paper, we briefly introduce white matter stroke from a clinical point of view and review pathophysiology of ischemic white matter injury characterized by OL death and demyelination...
August 2017: Experimental Neurobiology
https://www.readbyqxmd.com/read/28845299/enriched-housing-promotes-post-stroke-functional-recovery-through-astrocytic-hmgb1-il-6-mediated-angiogenesis
#2
Jia-Yi Chen, Yuan Yu, Yin Yuan, Yu-Jing Zhang, Xue-Peng Fan, Shi-Ying Yuan, Jian-Cheng Zhang, Shang-Long Yao
Enriched environment (EE) is shown to promote angiogenesis, neurogenesis and functional recovery after ischemic stroke. However, the underlying mechanisms remain unclear. C57BL/6 mice underwent middle cerebral artery occlusion (60 min) followed by reperfusion, after which mice were housed in either standard environment (SE) or EE. Here we found that post-ischemic EE exhibited decreased depression and anxiety-like behavior, and promoted angiogenesis and functional recovery compared to SE mice. EE mice treated with high-mobility group box-1 (HMGB1) inhibitor glycyrrhizin had an increased post-stroke depression and anxiety-like behavior, and the angiogenesis and functional recovery were decreased...
2017: Cell Death Discovery
https://www.readbyqxmd.com/read/28732809/oleacein-may-inhibit-destabilization-of-carotid-plaques-from-hypertensive-patients-impact-on-high-mobility-group-protein-1
#3
Agnieszka Filipek, Monika E Czerwińska, Anna K Kiss, Jerzy A Polański, Marek Naruszewicz
BACKGROUND: In patients with hypertension the haemorrhage into carotid atherosclerotic plaque increases risk of plaque destabilization and rupture. Our previous study showed that oleacein, a secoiridoid present in extra virgin olive oil, enhanced uptake of haemoglobin-haptoglobin complex and change macrophage phenotype from pro-inflammatory M1 to anti-inflammatory M2. PURPOSE: The aim this study was to investigate a potential role of oleacein in attenuation of carotid plaque destabilisation ex vivo...
August 15, 2017: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
https://www.readbyqxmd.com/read/28645523/elevated-serum-high-mobility-group-box-1-protein-level-is-associated-with-poor-functional-outcome-in-ischemic-stroke
#4
Toshiyuki Tsukagawa, Ryu Katsumata, Mitsugu Fujita, Keizo Yasui, Cassim Akhoon, Kenjiro Ono, Kenji Dohi, Toru Aruga
BACKGROUND: In experimental models, inhibition of high-mobility group box-1 (HMGB1) signaling has been reported to protect against the sequelae of ischemic stroke. Here, we determined the clinical significance of serum HMGB1 levels in patients with acute ischemic stroke. METHODS: We enrolled 183 patients (114 men, 69 women; mean age: 72.7 years) over 6 consecutive months. On admission and day 7, we recorded the National Institutes of Health Stroke Scale scores and measured serum high-sensitivity C-reactive protein (hs-CRP) and HMGB1 levels...
October 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28606778/hmgb1-promotes-neurovascular-remodeling-via-rage-in-the-late-phase-of-subarachnoid-hemorrhage
#5
Xiaodi Tian, Liang Sun, Dongxia Feng, Qing Sun, Yang Dou, Chenglin Liu, Feng Zhou, Haiying Li, Haitao Shen, Zhong Wang, Gang Chen
High-mobility group box1 (HMGB1) is a nuclear protein widely expressed in the central nervous system. Extracellular HMGB1 serves as a proinflammatory cytokine and contributes to brain injury during the acute stage post-stroke. Recently, increasing evidence has demonstrated beneficial effects of HMGB1 in some types of brain injury, but little is known about its effects during the late phase of subarachnoid hemorrhage (SAH). This study was designed to explore the potential roles and mechanisms of HMGB1 and its receptor, receptor for advanced glycation end-products (Rage), on brain recovery in the late stage of experimental SAH...
June 9, 2017: Brain Research
https://www.readbyqxmd.com/read/28584116/high-mobility-group-box-1-as-an-autocrine-trophic-factor-in-white-matter-stroke
#6
Jun Young Choi, Yuexian Cui, Samma Tasneem Chowdhury, Byung Gon Kim
Maintenance of white matter integrity in health and disease is critical for a variety of neural functions. Ischemic stroke in the white matter frequently results in degeneration of oligodendrocytes (OLs) and myelin. Previously, we found that toll-like receptor 2 (TLR2) expressed in OLs provides cell-autonomous protective effects on ischemic OL death and demyelination in white matter stroke. Here, we identified high-mobility group box-1 (HMGB1) as an endogenous TLR2 ligand that promotes survival of OLs under ischemic stress...
June 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28394332/mafb-prevents-excess-inflammation-after-ischemic-stroke-by-accelerating-clearance-of-damage-signals-through-msr1
#7
Takashi Shichita, Minako Ito, Rimpei Morita, Kyoko Komai, Yoshiko Noguchi, Hiroaki Ooboshi, Ryusuke Koshida, Satoru Takahashi, Tatsuhiko Kodama, Akihiko Yoshimura
Damage-associated molecular patterns (DAMPs) trigger sterile inflammation after tissue injury, but the mechanisms underlying the resolution of inflammation remain unclear. In this study, we demonstrate that common DAMPs, such as high-mobility-group box 1 (HMGB1), peroxiredoxins (PRXs), and S100A8 and S100A9, were internalized through the class A scavenger receptors MSR1 and MARCO in vitro. In ischemic murine brain, DAMP internalization was largely mediated by MSR1. An elevation of MSR1 levels in infiltrating myeloid cells observed 3 d after experimental stroke was dependent on the transcription factor Mafb...
June 2017: Nature Medicine
https://www.readbyqxmd.com/read/28393932/anti-high-mobility-group-box-1-hmgb1-antibody-inhibits-hemorrhage-induced-brain-injury-and-improved-neurological-deficits-in-rats
#8
Dengli Wang, Keyue Liu, Hidenori Wake, Kiyoshi Teshigawara, Shuji Mori, Masahiro Nishibori
As one of the most lethal stroke subtypes, intracerebral hemorrhage (ICH) is acknowledged as a serious clinical problem lacking effective treatment. Available evidence from preclinical and clinical studies suggests that inflammatory mechanisms are involved in the progression of ICH-induced secondary brain injury. High mobility group box-1 (HMGB1) is a ubiquitous and abundant nonhistone DNA-binding protein, and is also an important proinflammatory molecule once released into the extracellular space from the nuclei...
April 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28152042/effect-of-pregabalin-administration-upon-reperfusion-in-a-rat-model-of-hyperglycemic-stroke-mechanistic-insights-associated-with-high-mobility-group-box-1
#9
Young Song, Ji-Hae Jun, Eun-Jung Shin, Young-Lan Kwak, Jeon-Soo Shin, Jae-Kwang Shim
Hyperglycemia, which reduces the efficacy of treatments and worsens clinical outcomes, is common in stroke. Ability of pregabalin to reduce neuroexcitotoxicity may provide protection against stroke, even under hyperglycemia. We investigated its protective effect against hyperglycemic stroke and its possible molecular mechanisms. Male Wistar rats administered dextrose to cause hyperglycemia, underwent middle cerebral artery occlusion for 1 h and subsequent reperfusion. Rats were treated with an intraperitoneal injection of 30 mg/kg pregabalin or an equal amount of normal saline at the onset of reperfusion (n = 16 per group)...
2017: PloS One
https://www.readbyqxmd.com/read/27784773/leukocyte-response-is-regulated-by-microrna-let7i-in-patients-with-acute-ischemic-stroke
#10
Glen C Jickling, Bradley P Ander, Natasha Shroff, Miles Orantia, Boryana Stamova, Cheryl Dykstra-Aiello, Heather Hull, Xinhua Zhan, DaZhi Liu, Frank R Sharp
OBJECTIVE: To evaluate microRNA let7i in ischemic stroke and its regulation of leukocytes. METHODS: A total of 212 patients were studied: 106 with acute ischemic stroke and 106 controls matched for risk factors. RNA from circulating leukocytes was isolated from blood collected in PAXgene tubes. Let7i microRNA expression was assessed using TaqMan quantitative reverse transcription PCR. To assess let7i regulation of gene expression in stroke, messenger RNA (mRNA) from leukocytes was measured by whole-genome Human Transcriptome Array Affymetrix microarray...
November 22, 2016: Neurology
https://www.readbyqxmd.com/read/27609334/glycyrrhizin-protects-against-focal-cerebral-ischemia-via-inhibition-of-t-cell-activity-and-hmgb1-mediated-mechanisms
#11
Xiaoxing Xiong, Lijuan Gu, Yan Wang, Ying Luo, Hongfei Zhang, Jessica Lee, Sheri Krams, Shengmei Zhu, Heng Zhao
BACKGROUND: Glycyrrhizin (Gly) protects against brain injury induced by stroke. We studied whether Gly achieves its protection by inhibiting T cell activity and high-mobility group box 1 (HMGB1) release in the ischemic brain. METHODS: Stroke was induced by transient middle cerebral artery occlusion in rats and mice. Gly was injected intraperitoneally before or after stroke. We measured infarction, neuroinflammatory cells, gene expressions of interferon-γ (IFNγ), IL-4, and IL-10 in CD4 T cells, HMGB1 release, and T cell proliferation in cultured splenocytes...
September 8, 2016: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/27596007/inhibiting-hmgb1-reduces-cerebral-ischemia-reperfusion-injury-in-diabetic-mice
#12
Chong Wang, Jie Jiang, Xiuping Zhang, Linjie Song, Kai Sun, Ruxiang Xu
High mobility group box1 (HMGB1) promotes inflammatory injury, and accumulating evidence suggests that it plays a key role in brain ischemia reperfusion (I/R), as well as the development of diabetes mellitus (DM). The purpose of this study was to investigate whether HMGB1 plays a role in brain I/R in a DM mouse model. Diabetes mellitus was induced by a high-calorie diet and streptozotocin treatment, and cerebral ischemia was induced by middle cerebral artery occlusion. We examined HMGB1 levels following cerebral I/R injury in DM and non-DM mice and evaluated the influence of altered HMGB1 levels on the severity of cerebral injury...
December 2016: Inflammation
https://www.readbyqxmd.com/read/27544687/hypothermia-inhibits-the-propagation-of-acute-ischemic-injury-by-inhibiting-hmgb1
#13
Jung Ho Lee, Eun Jang Yoon, Jeho Seo, Adriana Kavoussi, Yong Eun Chung, Sung Phil Chung, Incheol Park, Chul Hoon Kim, Je Sung You
Acute ischemic stroke causes significant chronic disability worldwide. We designed this study to clarify the mechanism by which hypothermia helps alleviate acute ischemic stroke. In a middle cerebral artery occlusion model (4 h ischemia without reperfusion), hypothermia effectively reduces mean infarct volume. Hypothermia also prevents neurons in the infarct area from releasing high mobility group box 1 (HMGB1), the most well-studied damage-associated molecular pattern protein. By preventing its release, hypothermia also prevents the typical middle cerebral artery occlusion-induced increase in serum HMGB1...
2016: Molecular Brain
https://www.readbyqxmd.com/read/27501713/therapeutic-targeting-of-hmgb1-in-stroke
#14
Xiaodi Tian, Zhong Wang, Gang Chen
High mobility group box-1 (HMGB1), a highly conserved nonhistone nuclear protein, is widely expressed in most eukaryotic cells including neural cells. Nuclear HMGB1 stabilize nucleosome formation and facilitates gene transcription. HMGB1 can be passively released from necrotic cells or actively secreted from stimulated immune cells. Extracellular HMGB1 interacts with receptors, including the receptor for advanced glycation endproducts (RAGEs), Toll-like receptor 2 (TLR2) and TLR4. After brain injury, HMGB1 is released early from neural cells and contribute to the early stages of the inflammatory response...
August 8, 2016: Current Drug Delivery
https://www.readbyqxmd.com/read/27335313/possible-involvement-of-the-hmgb1-rage-signaling-mechanism-in-the-induction-of-central-post-stroke-pain-induced-by-acute-global-cerebral-ischemia
#15
Shinichi Harada, Wataru Matsuura, Keyue Liu, Masahiro Nishibori, Shogo Tokuyama
Central post-stroke pain (CPSP) is one of the most under-recognized consequences of cerebral stroke, but the development of an effective treatment strategy is urgent. High-mobility group box 1 (HMGB1) and the receptor for advanced glycation end products (RAGE, one of the receptors of HMGB1) have recently been shown to be critical in the modulation of nociceptive transduction following peripheral neuropathy. The aim of this study was to determine the interactions between CPSP and HMGB1/RAGE signaling. Male ddY mice were subjected to 30min of bilateral carotid artery occlusion (BCAO)...
September 1, 2016: Brain Research
https://www.readbyqxmd.com/read/27333763/-current-status-and-future-prospects-in-hmgb1-and-receptor-researches
#16
REVIEW
Hideo Takahashi, Masahiro Nishibori
High mobility group box protein1 (HMGB1), a ubiquitous chromatin component, is released by necrotic cells, apoptotic cells, and cells in profound distress. HMGB1 plays a critical role as a proinflammatory mediator. HMGB1 represents an important new target for drug development in a variety of inflammatory disorders, including stroke, brain injury, arteriosclerosis, and cancer. The antibodies against HMGB1 and its receptors ar hopeful candidates for immunotherapeutic strategy for treating patients with these diseases...
April 2016: Nihon Rinsho. Japanese Journal of Clinical Medicine
https://www.readbyqxmd.com/read/27126918/different-effects-of-arginine-vasopressin-on-high-mobility-group-box-1-expression-in-astrocytes-isolated-from-stroke-prone-spontaneously-hypertensive-rats-and-congenic-shrpch1_18-rats
#17
Kazuo Yamagata, Natumi Sone, Sari Suguyama, Toru Nabika
Stroke-prone spontaneously hypertensive rats (SHRSP/Izm) develop severe hypertension and astrocytic oedema following ischaemic stimulation. During ischaemic stress high-mobility group box 1 (Hmgb1) expression in astrocytes is induced, and subsequently potentiates deterioration of the brain due to ischaemic injury, which manifests as both cerebral inflammation and astrocytic oedema. Arginine vasopressin (AVP) induces brain injury and increases astrocytic swelling. After stroke, Hmgb1 and peroxiredoxin (Prx) are released at different times and activate macrophages in the brain via Toll-like receptors (Tlr2s)...
April 2016: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/27040385/activation-of-toll-like-receptors-2-by-high-mobility-group-box-1-in-monocytes-from-patients-with-ischemic-stroke
#18
Leila Sadat-Hatamnezhad, Asghar Tanomand, Javad Mahmoudi, Siamak Sandoghchian Shotorbani
BACKGROUND: Stroke is a leading cause of death all around the world, and ischemic stroke is considered to be the most common stroke type. Toll-like receptors (TLRs) are important molecules for detection of both pathogen invasion and tissue damage. In this regard, the purpose of this study was to assess the expression level of TLR2 on monocytes in patients with ischemic stroke and to evaluate the expression change profile following high-mobility group box 1 (HMGB1) stimulation. METHODS: A total of 30 patients with ischemic stroke were enrolled from November 2013 to September 2014...
September 2016: Iranian Biomedical Journal
https://www.readbyqxmd.com/read/26946264/bone-marrow-stromal-cells-inhibits-hmgb1-mediated-inflammation-after-stroke-in-type-2-diabetic-rats
#19
J Hu, B Liu, Q Zhao, P Jin, F Hua, Z Zhang, Y Liu, K Zan, G Cui, X Ye
High-mobility group box 1 (HMGB1), a ligand of receptor for advanced glycation endproducts (RAGE), functions as a proinflammatory factor. It is mainly involved in inflammatory activation and contributes to the initiation and progression of stroke. By using a model of transient middle cerebral artery occlusion (MCAo) in type 2 diabetic rats, we investigated the changes of pro-inflammation mediators, blood-brain barrier (BBB) leakage and functional outcome after stroke. Type 2 diabetic rats did not show an increased lesion volume, but exhibited significantly increased expression of HMGB1 and RAGE, BBB leakage, as well as decreased functional outcome after stroke compared with control rats...
June 2, 2016: Neuroscience
https://www.readbyqxmd.com/read/26944163/recombinant-human-soluble-thrombomodulin-ameliorates-cerebral-ischemic-injury-through-a-high-mobility-group-box-1-inhibitory-mechanism-without-hemorrhagic-complications-in-mice
#20
Yoshihiko Nakamura, Takafumi Nakano, Keiichi Irie, Kazunori Sano, Junichi Tanaka, Yuta Yamashita, Tomomitsu Satho, Koichi Matsuo, Masayuki Fujioka, Hiroyasu Ishikura, Kenichi Mishima
BACKGROUND: It has been reported that recombinant human soluble thrombomodulin (rhsTM) has a high-mobility group box (HMGB)1 inhibitory effect. Some investigators reported that HMGB1 is associated with ischemic stroke. However, there have been no previous studies to determine whether rhsTM can ameliorate cerebral ischemic injury through its HMGB1 inhibitory mechanism in ischemic stroke. We investigated the effects of rhsTM on cerebral ischemic injury in a 4-h middle cerebral artery occlusion (MCAO) murine model...
March 15, 2016: Journal of the Neurological Sciences
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