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Ischemic tolerance

Le Kang, Mingsan Miao
Objective: To observe the intervention effect of total flavonoid of ilex pubesceus on animal models of cerebral ischemic tolerance. Methods: A rat model of global-focal cerebral ischemic tolerance was established by blocking bilateral common carotid artery blood flow and occluding left middle cerebral artery using thread-occlusion method. After the first operation, the Ginaton group and large-dosage, medium-dosage and small-dosage groups of total flavonoid of ilex pubesceus were given intragastric administration of corresponding drugs...
December 2017: Saudi Journal of Biological Sciences
Le Kang, Mingsan Miao, Ming Bai, Shuo Tian
Objective: To study the protective effect of total flavonoid in rabdosia rubescens on BIT model by brain ischemic tolerance (hereinafter BIT) model of mice. Method: BIT model is used to block bilateral common carotid arteries and to copy BIT model of mice. After 10 min of transient ischemia for rats in preconditioning group, the mice in the nimodipine group and naoluotong capsule group were given the total flavonoid in rabdosia rubescens (300 mg/kg, 150 mg/kg, 75 mg/kg) for gavage, sham operation group, ischemia/reperfusion injury (hereinafter IRI) group and BIT group were fed with the same volume of 0...
December 2017: Saudi Journal of Biological Sciences
Fred Stephen Sarfo, Osei Sarfo-Kantanka, Sheila Adamu, Vida Obese, Jennifer Voeks, Raelle Tagge, Vipin Sethi, Bruce Ovbiagele
BACKGROUND: There is an unprecedented rise in the prevalence of stroke in sub-Saharan Africa (SSA). Secondary prevention guidelines recommend that antihypertensive, statin and antiplatelet therapy be initiated promptly after ischemic stroke and adhered to in a persistent fashion to achieve optimal vascular-risk reduction. However, these goals are seldom realized in routine clinical care settings in SSA due to logistical challenges. We seek to assess whether a polypill containing fixed doses of three antihypertensive agents, a statin and antiplatelet therapy taken once daily per os for 12 months among recent stroke survivors would result in carotid intimal thickness regression compared with usual care (UC)...
March 14, 2018: Trials
Michael Creane, Mary Mc Elroy, Aoife Duffy, Chaansha Shaik Dawood, Timothy O'Brien
Critical limb ischemia (CLI) represents the severest manifestation of peripheral arterial disease and is a major unmet medical need. This disease occurs when the arterial blood supply within the limb fails to meet the metabolic demands of the resting muscle or tissue, resulting in chronic ischemic rest pain and/or tissue necrosis. Human mesenchymal stromal cells, termed hMSCs, represent an exciting therapeutic modality for the treatment of this disease due to their immunomodulatory and tissue reparative functions...
January 1, 2018: Toxicologic Pathology
Konrad Kadzielawa, Biji Mathew, Clara R Stelman, Arden Zhengdeng Lei, Leianne Torres, Steven Roth
PURPOSE: The pathophysiology of retinal ischemia involves mechanisms including inflammation and apoptosis. Ischemic post-conditioning (Post-C), a brief non-lethal ischemia, induces a long-term ischemic tolerance, but the mechanisms of ischemic post-conditioning in the retina have only been described on a limited basis. Accordingly, we conducted this study to determine the molecular events in retinal ischemic post-conditioning and to identify targets for therapeutic strategies for retinal ischemia...
March 5, 2018: Graefe's Archive for Clinical and Experimental Ophthalmology
Sayed Masoud Hosseini, Hamid Gholami Pourbadie, Mohammad Sayyah, Mohammad Ismail Zibaii, Nima Naderi
Finding a neuroprotective strategy to rescue patients suffering from acute brain damage is of great interest. Monophosphoryl lipid A (MPL) is a derivative of lipopolysaccharide (LPS) that lacks many of the endotoxic properties of the parent molecule, and yet has similar protective effect. Here, we report the first evidence that MPL preconditioning, similar to LPS preconditioning, can induce neuroprotection against cerebral ischemia. MPL (0.5, 1, 5 µg/rat) was injected unilaterally into the left cerebral ventricle of male rats, and 48h later, rats were subjected to ipsilateral selective hippocampal ischemia using a modified version of the photothrombotic method...
March 1, 2018: Behavioural Brain Research
Brian Mac Grory, Shadi Yaghi
In this article, we discuss major advances in the treatment and prevention of ischemic stroke that have taken placed in the past 3 years. The most important advance in acute stroke treatment is the validation and widespread adoption of intra-arterial therapies for the treatment of acute ischemic stroke. Five clinical trials spanning multiple continents were published in early 2015 that proved that intra-arterial treatment - both with and without tPA - is beneficial in improving functional recovery after stroke...
March 1, 2018: Rhode Island Medical Journal
Michael Koeppen, Jae W Lee, Seong-Wook Seo, Kelley S Brodsky, Simone Kreth, Ivana V Yang, Peter M Buttrick, Tobias Eckle, Holger K Eltzschig
Myocardial ischemia-reperfusion injury (IRI) leads to the stabilization of the transcription factors hypoxia-inducible factor 1-alpha (HIF1-alpha) and hypoxia-inducible factor 2-alpha (HIF2-alpha). While previous studies implicate HIF1-alpha in cardioprotection, the role of HIF2-alpha remains elusive. Here we show that HIF2-alpha induces the epithelial growth factor amphiregulin (AREG) to elicit cardioprotection in myocardial IRI. Comparing mice with inducible deletion of Hif1a or Hif2a in cardiac myocytes, we show that loss of Hif2-alpha increases infarct sizes...
February 26, 2018: Nature Communications
Hassan Khan, Setor K Kunutsor, Rainer Rauramaa, Faisal M Merchant, Jari A Laukkanen
The benefits of aerobic fitness in relation to all-cause and cardiovascular mortality is well established; however, the associations of long-term change in cardiorespiratory fitness (CRF) with incident heart failure (HF) and atrial fibrillation (AF) have not been studied before. The Kuopio Ischaemic Heart Disease Risk Factor Study is a prospective cohort comprising men aged 42 to 60 years from the city of Kuopio and its surroundings, with a baseline examination between 1984 and 1989 (V1), a re-examination at 11 years (V2), and up to 15 years of follow-up from V2...
February 2, 2018: American Journal of Cardiology
Hidetoshi Tsuda, Charles A Su, Toshiaki Tanaka, Katayoun Ayasoufi, Booki Min, Anna Valujskikh, Robert L Fairchild
Recipient endogenous memory T cells with donor reactivity pose an important barrier to successful transplantation and costimulatory blockade-induced graft tolerance. Longer ischemic storage times prior to organ transplantation increase early posttransplant inflammation and negatively impact early graft function and long-term graft outcome. Little is known about the mechanisms enhancing endogenous memory T cell activation to mediate tissue injury within the increased inflammatory environment of allografts subjected to prolonged cold ischemic storage (CIS)...
February 22, 2018: JCI Insight
Byong Sop Lee, Dong-Cheol Woo, Chul-Woong Woo, Ki-Soo Kim
β-Hydroxybutyrate (BHB) is a representative ketone body that may play a role in the mitigation of neonatal hypoxic-ischemic encephalopathy by altering energy metabolism. This study aimed to investigate the neuroprotective efficacy of exogenous BHB administration in a suckling rat model after hypoxia-ischemia (HI). Thirteen-day-old (P13) rat pups were subjected to 120 min of hypoxia according to the Rice-Vannucci model. BHB (5.0 mmol/kg, HI-BHB) or vehicle (0.9% saline, HI-Veh) was administered 0, 2, 4, and 6 h after HI induction...
February 21, 2018: Developmental Neuroscience
Setayesh R Tasbihgou, Mina Netkova, Alain F Kalmar, Janine Doorduin, Michel M R F Struys, Regien G Schoemaker, Anthony R Absalom
In anaesthetic practice the risk of cerebral ischemic/hypoxic damage is thought to be attenuated by deep anaesthesia. The rationale is that deeper anaesthesia reduces cerebral oxygen demand more than light anaesthesia, thereby increasing the tolerance to ischemia or hypoxia. However, evidence to support this is scarce. We thus investigated the influence of light versus deep anaesthesia on the responses of rat brains to a period of hypoxia. In the first experiment we exposed adult male Wistar rats to deep or light propofol anaesthesia and then performed [18F]- Fludeoxyglucose (FDG) Positron Emission Tomography (PET) scans to verify the extent of cerebral metabolic suppression...
2018: PloS One
Olivia Sanchez, Andrea García, Fernando Castro-Prado, Miriam Perez, Rafael Lara-Estrada, Martin Ramirez-Meza, Montserrat Godinez, Michael L Coco, Joaquín Azpiroz, Mark K Borsody, Emilio Sacristán
BACKGROUND: Magnetic stimulation of the facial nerve has been tested in preclinical studies as a new, non-invasive emergency treatment of ischemic stroke that acts by increasing cerebral blood flow (CBF). The objective of the studies reported herein was to identify minimal stimulation parameters that increase CBF in large animals and then test those stimulation parameters in healthy volunteers for safety, tolerability, and effectiveness at increasing CBF. This translational research is necessary preparation for clinical studies in ischemic stroke patients...
February 15, 2018: Journal of Translational Medicine
Annemarie Wentzel, Leoné Malan, Jacobus D Scheepers, Nicolaas T Malan
Alcohol contributes greatly to vascular and structural modifications. Due to differences in the metabolism and tolerance of alcohol between ethnic groups, the manner of these modifications may differ. We investigated the association between alcohol consumption - measured via ethnic-specific gamma glutamyl transferase (γ-GT) cut-points - and markers of cardiac perfusion, electrical activity, and pre-clinical structural alterations. A South African target population study was performed in a bi-ethnic cohort (n = 405)...
September 14, 2017: Alcohol
Clément Gauvain, Enora Vauléon, Christos Chouaid, Emilie Lerhun, Laurence Jabot, Arnaud Scherpereel, Florent Vinas, Alexis Benjamin Cortot, Isabelle Monnet
OBJECTIVES: Although nivolumab has shown efficacy against non-small-cell lung cancers (NSCLCs), patients with active brain metastases (BMs) were excluded from pivotal clinical trials. Hence, data regarding nivolumab intracerebral activity and safety in NSCLC patients with BMs are scarce. MATERIALS AND METHODS: We conducted a retrospective multicenter study on NSCLC patients with BMs treated with nivolumab. The primary endpoint was intracerebral objective response rate (IORR), according to RECIST criteria...
February 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Lin Wang, Nanhu Quan, Wanqing Sun, Xu Chen, Courtney Cates, Thomas Rousselle, Xinchun Zhou, Xuezhong Zhao, Ji Li
Aim: A longevity gene, Sirtuin 1 (SIRT1) and energy sensor AMP-activated protein kinase (AMPK) have common activators such as caloric restriction, oxidative stress and exercise. The objective of this study is to characterize the role of cardiomyocyte SIRT1 in age-related impaired ischemic AMPK activation and increased susceptibility to ischemic insults. Methods and Results: Mice were subjected to ligation of left anterior descending coronary artery for in vivo ischemic models...
February 2, 2018: Cardiovascular Research
James M Mathew, Mohammed Javeed Ansari, Lorenzo Gallon, Joseph R Leventhal
Development of tolerance protocols requires assays or biomarkers that distinguish tolerant recipients from non-tolerant ones to be established. In addition, a thorough understanding of the plausible mechanisms associated with clinical transplant tolerance is necessary to take the field forward. Unlike the majority of molecular signature analyses utilized by others, the emphasis of this article is on the cellular and functional biomarkers of induced transplant tolerance. Immunity to an organ transplant is very complex, comprised of two broad categories - innate and acquired or adaptive immune responses...
January 25, 2018: Human Immunology
Rebeca Vecino, Maria C Burguete, Teresa Jover-Mengual, Jesus Agulla, Verónica Bobo-Jiménez, Juan B Salom, Angeles Almeida, Maria Delgado-Esteban
Brain preconditioning (PC) refers to a state of transient tolerance against a lethal insult that can be evoked by a prior mild event. It is thought that PC may induce different pathways responsible for neuroprotection, which may involve the attenuation of cell damage pathways, including the apoptotic cell death. In this context, p53 is a stress sensor that accumulates during brain ischemia leading to neuronal death. The murine double minute 2 gene (MDM2), a p53-specific E3 ubiquitin ligase, is the main cellular antagonist of p53, mediating its degradation by the proteasome...
January 25, 2018: Scientific Reports
Srinivasan V Narayanan, Miguel A Perez-Pinzon
Ischemic preconditioning (IPC) represents a potential therapy against cerebral ischemia. While our group has previously shown IPC to induce neuroprotection through various pathways, the role of astrocytes in supporting IPC-induced neuroprotection has not been extensively studied. Astrocyte-derived lactate has gained attention as a potential soluble mediator through which astrocytes could impart ischemic tolerance to neurons. Therefore, the goal of this study was to determine if i) IPC-treatment of astrocytes alone could transfer ischemic tolerance to neurons; ii) if IPC-treatment of astrocytes increases lactate production; and if iii) exogenous lactate administration to neurons could induce neuroprotection against lethal ischemia in vitro...
December 2017: Cond Med
Raisa Yu Kiseleva, C F Greineder, C H Villa, O A Marcos-Contreras, E D Hood, V V Shuvaev, H M DeLisser, V R Muzykantov
Targeting drugs to endothelial cells has shown the ability to improve outcomes in animal models of inflammatory, ischemic and thrombotic diseases. Previous studies have revealed that certain pairs of ligands (antibodies and antibody fragments) specific for adjacent, but distinct, epitopes on PECAM-1 enhance each other's binding, a phenomenon dubbed Collaborative Enhancement of Paired Affinity Ligands, or CEPAL. This discovery has been leveraged to enable simultaneous delivery of multiple therapeutics to the vascular endothelium...
January 24, 2018: Scientific Reports
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