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Xenon neuroprotection

Melvin E Klegerman, Melanie R Moody, Jermaine R Hurling, Tao Peng, Shao-Ling Huang, David D McPherson
RATIONALE: We have produced a liposomal formulation of xenon (Xe-ELIP) as a neuroprotectant for inhibition of brain damage in stroke patients. This mandates development of a reliable assay to measure the amount of dissolved xenon released from Xe-ELIP in water and blood samples. METHODS: Gas chromatography-Mass Spectrometry (GC-MS) was used to quantify xenon gas released into the headspace of vials containing Xe-ELIP samples in water or blood. In order to determine blood concentration of xenon in vivo after Xe-ELIP administration, 6 mg Xe-ELIP lipid was infused intravenously into rats...
September 30, 2016: Rapid Communications in Mass Spectrometry: RCM
J Lavaur, M Lemaire, J Pype, D Le Nogue, E C Hirsch, P P Michel
Noble gases such as xenon and argon have been reported to provide neuroprotection against acute brain ischemic/anoxic injuries. Herein, we wished to evaluate the protective potential of these two gases under conditions relevant to the pathogenesis of chronic neurodegenerative disorders. For that, we established cultures of neurons typically affected in Alzheimer's disease (AD) pathology, that is, cortical neurons and basal forebrain cholinergic neurons and exposed them to L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) to generate sustained, low-level excitotoxic stress...
2016: Cell Death Discovery
Shiyao Liu, Yanwei Yang, Mu Jin, Siyu Hou, Xiuhua Dong, Jiakai Lu, Weiping Cheng
Previous studies have shown that xenon-delayed postconditioning for up to 2h after reperfusion provides protection against spinal cord ischemia/reperfusion (I/R) injury in rats. This study was designed to determine the roles of phosphatidylinositol 3-kinase (PI3K)-Akt and extracellular signal-regulated kinase (ERK) in this neuroprotection. The rats were randomly assigned to the following nine groups (n=16∗9): 1) I/R+N2 group, 2) I/R+Xe group, 3) I/R+PD98059+N2 group (ERK blocking agent), 4) I/R+wortmannin+N2 group (PI3K-Akt blocking agent), 5) I/R+PD98059+Xe group, 6) I/R+wortmannin+Xe group, 7) I/R+DMSO+Xe group (dimethyl sulfoxide, vehicle control), 8) I/R+DMSO+N2 group, and 9) sham group (no spinal cord ischemia and no xenon)...
September 15, 2016: Journal of the Neurological Sciences
Hemmen Sabir, Damjan Osredkar, Elke Maes, Thomas Wood, Marianne Thoresen
BACKGROUND: Therapeutic hypothermia (TH) is standard treatment following perinatal asphyxia in newborn infants. Experimentally, TH is neuroprotective after moderate hypoxia-ischemia (HI) in seven-day-old (P7) rats. However, TH is not neuroprotective after severe HI. After a moderate HI insult in newborn brain injury models, the anesthetic gas xenon (Xe) doubles TH neuroprotection. The aim of this study was to examine whether combining Xe and TH is neuroprotective as applied in a P7 rat model of severe HI...
2016: PloS One
Julie De Deken, Steffen Rex, Diethard Monbaliu, Jacques Pirenne, Ina Jochmans
OBJECTIVE: Noble gases have been attributed to organ protective effects in ischemia reperfusion injury in a variety of medical conditions, including cerebral and cardiac ischemia, acute kidney injury, and transplantation. The aim of this study was to appraise the available evidence by systematically reviewing the literature and performing meta-analyses. DATA SOURCES: PubMed, EMBASE, and the Cochrane Library. STUDY SELECTION: Inclusion criteria specified any articles on noble gases and either ischemia reperfusion injury or transplantation...
September 2016: Critical Care Medicine
J Lavaur, M Lemaire, J Pype, D Le Nogue, E C Hirsch, P P Michel
No abstract text is available yet for this article.
2016: Cell Death & Disease
Patrick Zuercher, Dirk Springe, Denis Grandgirard, Stephen L Leib, Marius Grossholz, Stephan Jakob, Jukka Takala, Matthias Haenggi
BACKGROUND: The noble gas xenon is considered as a neuroprotective agent, but availability of the gas is limited. Studies on neuroprotection with the abundant noble gases helium and argon demonstrated mixed results, and data regarding neuroprotection after cardiac arrest are scant. We tested the hypothesis that administration of 50% helium or 50% argon for 24 h after resuscitation from cardiac arrest improves clinical and histological outcome in our 8 min rat cardiac arrest model. METHODS: Forty animals had cardiac arrest induced with intravenous potassium/esmolol and were randomized to post-resuscitation ventilation with either helium/oxygen, argon/oxygen or air/oxygen for 24 h...
2016: BMC Neurology
Hemmen Sabir, Thomas Wood, Hannah Gill, Xun Liu, John Dingley, Marianne Thoresen
BACKGROUND: Changes in electroencephalography (EEG) voltage range are used to monitor the depth of anaesthesia, as well as predict outcome after hypoxia-ischaemia in neonates. Xenon is being investigated as a potential neuroprotectant after hypoxic-ischaemic brain injury, but the effect of Xenon on EEG parameters in children or neonates is not known. This study aimed to examine the effect of 50% inhaled Xenon on background amplitude-integrated EEG (aEEG) activity in sedated healthy newborn pigs...
April 15, 2016: Journal of the Neurological Sciences
Ruut Laitio, Marja Hynninen, Olli Arola, Sami Virtanen, Riitta Parkkola, Jani Saunavaara, Risto O Roine, Juha Grönlund, Emmi Ylikoski, Johanna Wennervirta, Minna Bäcklund, Päivi Silvasti, Eija Nukarinen, Marjaana Tiainen, Antti Saraste, Mikko Pietilä, Juhani Airaksinen, Leena Valanne, Juha Martola, Heli Silvennoinen, Harry Scheinin, Veli-Pekka Harjola, Jussi Niiranen, Kirsi Korpi, Marjut Varpula, Outi Inkinen, Klaus T Olkkola, Mervyn Maze, Tero Vahlberg, Timo Laitio
IMPORTANCE: Evidence from preclinical models indicates that xenon gas can prevent the development of cerebral damage after acute global hypoxic-ischemic brain injury but, thus far, these putative neuroprotective properties have not been reported in human studies. OBJECTIVE: To determine the effect of inhaled xenon on ischemic white matter damage assessed with magnetic resonance imaging (MRI). DESIGN, SETTING, AND PARTICIPANTS: A randomized single-blind phase 2 clinical drug trial conducted between August 2009 and March 2015 at 2 multipurpose intensive care units in Finland...
March 15, 2016: JAMA: the Journal of the American Medical Association
Camille Tassel, Brendan Le Daré, Isabelle Morel, Thomas Gicquel
Doping is defined as the use of processes or substances to artificially increase physical or mental performance. Xenon is a noble gas used as an anesthetic and recently as a doping agent. Xenon is neuroprotective as an antagonist of NMDA glutamate receptors. Xenon stimulates the synthesis of erythropoietin (EPO) by increase of hypoxia inducible factor (HIF). Xenon would be a new doping product, maintaining doping methods ahead of detection.
April 2016: La Presse Médicale
Denis Azzopardi, Nicola J Robertson, Alan Bainbridge, Ernest Cady, Geoffrey Charles-Edwards, Aniko Deierl, Gianlorenzo Fagiolo, Nicholas P Franks, James Griffiths, Joseph Hajnal, Edmund Juszczak, Basil Kapetanakis, Louise Linsell, Mervyn Maze, Omar Omar, Brenda Strohm, Nora Tusor, A David Edwards
BACKGROUND: Moderate cooling after birth asphyxia is associated with substantial reductions in death and disability, but additional therapies might provide further benefit. We assessed whether the addition of xenon gas, a promising novel therapy, after the initiation of hypothermia for birth asphyxia would result in further improvement. METHODS: Total Body hypothermia plus Xenon (TOBY-Xe) was a proof-of-concept, randomised, open-label, parallel-group trial done at four intensive-care neonatal units in the UK...
December 18, 2015: Lancet Neurology
Benoit Haelewyn, Hélène N David, Jean-Eric Blatteau, Nicolas Vallée, Cedric Meckler, Jean-Jacques Risso, Jacques H Abraini
INTERVENTIONS: Helium has been shown to provide neuroprotection in mechanical model of acute ischemic stroke by inducing hypothermia, a condition shown by itself to reduce the thrombolytic and proteolytic properties of tissue plasminogen activator. However, whether or not helium interacts with the thrombolytic drug tissue plasminogen activator, the only approved therapy of acute ischemic stroke still remains unknown. This point is not trivial since previous data have shown the critical importance of the time at which the neuroprotective noble gases xenon and argon should be administered, during or after ischemia, in order not to block tissue plasminogen activator-induced thrombolysis and to obtain neuroprotection and inhibition of tissue plasminogen activator-induced brain hemorrhages...
June 2016: Critical Care Medicine
Mervyn Maze
PURPOSE: The purpose of this report is to facilitate an understanding of the possible application of xenon for neuroprotection in critical care settings. This narrative review appraises the literature assessing the efficacy and safety of xenon in preclinical models of acute ongoing neurologic injury. SOURCE: Databases of the published literature (MEDLINE® and EMBASE™) were appraised for peer-reviewed manuscripts addressing the use of xenon in both preclinical models and disease states of acute ongoing neurologic injury...
February 2016: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
Jean-Eric Blatteau, Hélène N David, Nicolas Vallée, Cedric Meckler, Sebastien Demaistre, Kate Lambrechts, Jean-Jacques Risso, Jacques H Abraini
Despite state-of-the-art hyperbaric oxygen (HBO) treatment, about 30% of patients suffering neurologic decompression sickness (DCS) exhibit incomplete recovery. Since the mechanisms of neurologic DCS involve ischemic processes which result in excitotoxicity, it is likely that HBO in combination with an anti-excitotoxic treatment would improve the outcome in patients being treated for DCS. Therefore, in the present study, we investigated the effect of the noble gas xenon in an ex vivo model of neurologic DCS...
2015: Scientific Reports
Layth Al Tmimi, Marc Van de Velde, Paul Herijgers, Bart Meyns, Geert Meyfroidt, Koen Milisen, Steffen Fieuws, Mark Coburn, Koen Poesen, Steffen Rex
BACKGROUND: Postoperative delirium (POD) is a manifestation of acute postoperative brain dysfunction that is frequently observed after cardiac surgery. POD is associated with short-term complications such as an increase in mortality, morbidity, costs and length of stay, but can also have long-term sequelae, including persistent cognitive deficits, loss of independence, and increased mortality for up to 2 years. The noble gas xenon has been demonstrated in various models of neuronal injury to exhibit remarkable neuroprotective properties...
2015: Trials
Joanne O Davidson, Guido Wassink, Lotte G van den Heuij, Laura Bennet, Alistair J Gunn
Hypoxia-ischemia before or around the time of birth occurs in approximately 2/1000 live births and is associated with a high risk of death or lifelong disability. Therapeutic hypothermia is now well established as standard treatment for infants with moderate to severe hypoxic-ischemic encephalopathy but is only partially effective. There is compelling preclinical and clinical evidence that hypothermia is most protective when it is started as early as possible after hypoxia-ischemia. Further improvements in outcome from therapeutic hypothermia are very likely to arise from strategies to reduce the delay before starting treatment of affected infants...
2015: Frontiers in Neurology
Brandon J Dixon, Cesar Reis, Wing Mann Ho, Jiping Tang, John H Zhang
Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates...
2015: International Journal of Molecular Sciences
A V Fahlenkamp, R Rossaint, M Coburn
Noble gases are chemically inert elements, some of which exert biological activity. Experimental neuroprotection in particular has been widely shown for xenon, argon and helium. The underlying mechanisms of action are not yet fully understood. Besides an interference with neuronal ion-gated channels and cellular signaling pathways as well as anti-apoptotic effects, the modulation of neuroinflammation seems to play a crucial role. This review presents the current knowledge on neuroprotection by noble gases with a focus on interactions with the neuronal-glial network and neuroinflammation and the perspectives on clinical applications...
November 2015: Der Anaesthesist
Kasper J Kyng, Torjus Skajaa, Sigrid Kerrn-Jespersen, Christer S Andreassen, Kristine Bennedsgaard, Tine B Henriksen
Birth asphyxia, which causes hypoxic-ischemic encephalopathy (HIE), accounts for 0.66 million deaths worldwide each year, about a quarter of the world's 2.9 million neonatal deaths. Animal models of HIE have contributed to the understanding of the pathophysiology in HIE, and have highlighted the dynamic process that occur in brain injury due to perinatal asphyxia. Thus, animal studies have suggested a time-window for post-insult treatment strategies. Hypothermia has been tested as a treatment for HIE in pdiglet models and subsequently proven effective in clinical trials...
2015: Journal of Visualized Experiments: JoVE
Sarah Devroe, Jurgen Lemiere, Marc Van de Velde, Marc Gewillig, Derize Boshoff, Steffen Rex
BACKGROUND: Xenon has minimal haemodynamic side effects when compared to volatile or intravenous anaesthetics. Moreover, in in vitro and in animal experiments, xenon has been demonstrated to convey cardio- and neuroprotective effects. Neuroprotection could be advantageous in paediatric anaesthesia as there is growing concern, based on both laboratory studies and retrospective human clinical studies, that anaesthetics may trigger an injury in the developing brain, resulting in long-lasting neurodevelopmental consequences...
2015: Trials
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