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Xenon neuroprotection

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https://www.readbyqxmd.com/read/29627444/inhalational-anesthetics-accelerate-desensitization-of-acid-sensing-ion-channels
#1
Linda Lehmke, Mark Coburn, Manfred Möller, Rosmarie Blaumeiser-Debarry, Pia Lenzig, Dominik Wiemuth, Stefan Gründer
Acid-sensing ion channels (ASICs) are neuronal Na+ channels that are activated by extracellular acidification. Inhibiting ASICs is neuroprotective in mouse models of ischemic stroke. As inhalational anesthetics interact with many ion channels and as some of them have neuroprotective effects, we hypothesized that inhalational anesthetics modulate ASICs. We expressed different homo- and heteromeric ASICs heterologously in Xenopus oocytes. We co-applied with acidic pH the halogenated inhalational anesthetics sevoflurane, desflurane, and isoflurane and the noble gases xenon and argon at concentrations that are roughly equivalent to their minimal alveolar concentrations and analyzed their effect on current kinetics and amplitude...
April 5, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29623938/delayed-xenon-post-conditioning-mitigates-spinal-cord-ischemia-reperfusion-injury-in-rabbits-by-regulating-microglial-activation-and-inflammatory-factors
#2
Yan-Wei Yang, Yun-Lu Wang, Jia-Kai Lu, Lei Tian, Mu Jin, Wei-Ping Cheng
The neuroprotective effect against spinal cord ischemia/reperfusion injury in rats exerted by delayed xenon post-conditioning is stronger than that produced by immediate xenon post-conditioning. However, the mechanisms underlying this process remain unclear. Activated microglia are the main inflammatory cell type in the nervous system. The release of pro-inflammatory factors following microglial activation can lead to spinal cord damage, and inhibition of microglial activation can relieve spinal cord ischemia/reperfusion injury...
March 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29608502/xenon-an-emerging-neuroprotectant-with-potential-application-for-cardiac-arrest-care
#3
Mohammad Roostan, William H Frishman
Xenon is an inert, highly polarizable noble gas with demonstrated safety and application in general anesthesia for over fifty years. A potent inhibitor of the N-methyl-D-aspartate subtype of glutamate receptors, xenon has a well-documented ameliorating effect on excitotoxic neuronal injury in numerous cellular and animal models of hypoxic-ischemic brain injury. The most important determinant of overall survival and morbidity in out-of-hospital cardiac arrest is the severity of neurological injury. The only approved neuroprotective strategy in this setting is mild therapeutic hypothermia, which has demonstrated significant, albeit modest, improvements in mortality...
March 30, 2018: Cardiology in Review
https://www.readbyqxmd.com/read/29588034/methods-for-defining-the-neuroprotective-properties-of-xenon
#4
Richie Robel, Peter Caroccio, Mervyn Maze
Xenon has features that make it an ideal general anesthetic agent; cost and scarcity mitigate xenon's widespread use in the operating room. Discovery of xenon's cytoprotective properties resulted in its application to thwart ongoing acute neurologic injury, an unmet clinical need. The discovery that xenon's neuroprotective effect interacts synergistically with targeted temperature management (TTM) led to its investigation in clinical settings, including in the management of the postcardiac arrest syndrome, in which TTM is indicated...
2018: Methods in Enzymology
https://www.readbyqxmd.com/read/29518790/impact-of-xenon-on-clic4-and-bcl-2-expression-in-lipopolysaccharide-and-hypoxia-ischemia-induced-periventricular-white-matter-damage
#5
Xiangyun Yin, Jixiu Zhao, Hong Jiang, Liangliang Li, Jian Jiang, Hongmin Xi, Xiangli Peng, Xiaohang Yin, Xiaotong Shi, Lulu Zhang
BACKGROUND: Premature birth is a significant health care burden. Xenon (Xe) is a general anesthetic with neuroprotective effects. OBJECTIVES: Here, we investigate the neuroprotective role of Xe in a lipopolysaccharide (LPS)- and hypoxia-ischemia (HI)-induced white matter damage (WMD) model. METHODS: Three-day-old Sprague-Dawley rats were randomly divided into a sham group (group A, n = 24), an LPS + HI group (group B, n = 24), and an LPS + HI + Xe group (group C, n = 72)...
March 8, 2018: Neonatology
https://www.readbyqxmd.com/read/29497489/the-role-of-nitrous-oxide-in-stroke
#6
REVIEW
Zhu-Wei Zhang, Dong-Ping Zhang, Hai-Ying Li, Zhong Wang, Gang Chen
Stroke that is caused by poor blood flow into the brain results in cell death, including ischemia stroke due to lack of blood into brain tissue, and hemorrhage due to bleeding. Both of them will give rise to the dysfunction of brain. In general, the signs and symptoms of stroke are the inability of feeling or moving on one side of body, sometimes loss of vision to one side. Above symptoms will appear soon after the stroke has happened. If the symptoms and signs happen in 1 or 2 hours, we often call them as transient ischemic attack...
October 2017: Medical Gas Research
https://www.readbyqxmd.com/read/29452802/moving-to-human-trials-for-argon-neuroprotection-in-neurological-injury-a-narrative-review
#7
REVIEW
A J Gardner, D K Menon
Despite the global burden of brain injury, neuroprotective agents remain elusive. There are no clinically effective therapies which reduce mortality or improve long-term cognitive outcome. Ventilation could be an easily modifiable variable in resuscitation; gases are relatively simple to administer. Xenon is the prototypic agent of a new generation of experimental treatments which show promise. However, use is hindered by its prohibitive cost and anaesthetic properties. Argon is an attractive option, being cheaper, easy to transport, non-sedating, and mechanistically distinct from xenon...
March 2018: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29397119/the-hip-fracture-surgery-in-elderly-patients-hipeld-study-to-evaluate-xenon-anaesthesia-for-the-prevention-of-postoperative-delirium-a-multicentre-randomized-clinical-trial
#8
M Coburn, R D Sanders, M Maze, M-L Nguyên-Pascal, S Rex, B Garrigues, J A Carbonell, M L Garcia-Perez, A Stevanovic, P Kienbaum, M Neukirchen, M S Schaefer, B Borghi, H van Oven, A Tognù, L Al Tmimi, L Eyrolle, O Langeron, X Capdevila, G M Arnold, M Schaller, R Rossaint
BACKGROUND: Postoperative delirium occurs frequently in elderly hip fracture surgery patients and is associated with poorer overall outcomes. Because xenon anaesthesia has neuroprotective properties, we evaluated its effect on the incidence of delirium and other outcomes after hip fracture surgery. METHODS: This was a phase II, multicentre, randomized, double-blind, parallel-group, controlled clinical trial conducted in hospitals in six European countries (September 2010 to October 2014)...
January 2018: British Journal of Anaesthesia
https://www.readbyqxmd.com/read/29323183/delivery-of-xenon-containing-echogenic-liposomes-inhibits-early-brain-injury-following-subarachnoid-hemorrhage
#9
Yi-Feng Miao, Tao Peng, Melanie R Moody, Melvin E Klegerman, Jaroslaw Aronowski, James Grotta, David D McPherson, Hyunggun Kim, Shao-Ling Huang
Xenon (Xe), a noble gas, has promising neuroprotective properties with no proven adverse side-effects. We evaluated neuroprotective effects of Xe delivered by Xe-containing echogenic liposomes (Xe-ELIP) via ultrasound-controlled cerebral drug release on early brain injury following subarachnoid hemorrhage (SAH). The Xe-ELIP structure was evaluated by ultrasound imaging, electron microscopy and gas chromatography-mass spectroscopy. Animals were randomly divided into five groups: Sham, SAH, SAH treated with Xe-ELIP, empty ELIP, or Xe-saturated saline...
January 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29285980/xenon-protects-against-blast-induced-traumatic-brain-injury-in-an-in-vitro-model
#10
Rita Campos-Pires, Mariia Koziakova, Amina Yonis, Ashni Pau, Warren Macdonald, Katie Harris, Christopher J Edge, Nicholas P Franks, Peter F Mahoney, Robert Dickinson
The aim of this study was to evaluate the neuroprotective efficacy of the inert gas xenon as a treatment for patients with blast-induced traumatic brain injury in an in vitro laboratory model. We developed a novel blast traumatic brain injury model using C57BL/6N mouse organotypic hippocampal brain-slice cultures exposed to a single shockwave, with the resulting injury quantified using propidium iodide fluorescence. A shock tube blast generator was used to simulate open field explosive blast shockwaves, modeled by the Friedlander waveform...
February 8, 2018: Journal of Neurotrauma
https://www.readbyqxmd.com/read/29152211/xenon-helium-gas-mixture-at-equimolar-concentration-of-37-5-protects-against-oxygen-and-glucose-deprivation-induced-injury-and-inhibits-tissue-plasminogen-activator
#11
Hélène N David, Benoit Haelewyn, Jean-Éric Blatteau, Jean-Jacques Risso, Nicolas Vallée, Jacques H Abraini
Xenon (Xe) is considered to be the golden standard neuroprotective gas. However, Xe has a higher molecular weight and lower thermal conductivity and specific heat than those of nitrogen, the main diluent of oxygen in air. These physical characteristics could impair or at least reduce the intrinsic neuroprotective action of Xe by increasing the patient's respiratory workload and body temperature. In contrast, helium (He) is a cost-efficient gas with a lower molecular weight and higher thermal conductivity and specific heat than those of nitrogen, but is far less potent than Xe...
July 2017: Medical Gas Research
https://www.readbyqxmd.com/read/29152210/a-method-for-calculating-the-gas-volume-proportions-and-inhalation-temperature-of-inert-gas-mixtures-allowing-reaching-normothermic-or-hypothermic-target-body-temperature-in-the-awake-rat
#12
Jacques H Abraini, Hélène N David, Jean-Éric Blatteau, Jean Jacques Risso, Nicolas Vallée
The noble gases xenon (Xe) and helium (He) are known to possess neuroprotective properties. Xe is considered the golden standard neuroprotective gas. However, Xe has a higher molecular weight and lower thermal conductivity and specific heat than those of nitrogen, the main diluent of oxygen (O2) in air, conditions that could impair or at least reduce the intrinsic neuroprotective properties of Xe by increasing the critical care patient's respiratory workload and body temperature. In contrast, He has a lower molecular weight and higher thermal conductivity and specific heat than those of nitrogen, but is unfortunately far less potent than Xe at providing neuroprotection...
July 2017: Medical Gas Research
https://www.readbyqxmd.com/read/29108649/mapping-hydrophobic-tunnels-and-cavities-in-neuroglobin-with-noble-gas-under-pressure
#13
Nathalie Colloc'h, Philippe Carpentier, Laura C Montemiglio, Beatrice Vallone, Thierry Prangé
Internal cavities are crucial for conformational flexibility of proteins and can be mapped through noble gas diffusion and docking. Here we investigate the hydrophobic cavities and tunnel network in neuroglobin (Ngb), a hexacoordinated heme protein likely to be involved in neuroprotection, using crystallography under noble gas pressure, mostly at room temperature. In murine Ngb, a large internal cavity is involved in the heme sliding mechanism to achieve binding of gaseous ligands through coordination to the heme iron...
November 21, 2017: Biophysical Journal
https://www.readbyqxmd.com/read/29021779/xenon-reduces-neuronal-hippocampal-damage-and-alters-the-pattern-of-microglial-activation-after-experimental-subarachnoid-hemorrhage-a-randomized-controlled-animal-trial
#14
Michael Veldeman, Mark Coburn, Rolf Rossaint, Hans Clusmann, Kay Nolte, Benedikt Kremer, Anke Höllig
OBJECTIVE: The neuroprotective properties of the noble gas xenon have already been demonstrated using a variety of injury models. Here, we examine for the first time xenon's possible effect in attenuating early brain injury (EBI) and its influence on posthemorrhagic microglial neuroinflammation in an in vivo rat model of subarachnoid hemorrhage (SAH). METHODS: Sprague-Dawley rats ( n  = 22) were randomly assigned to receive either Sham surgery ( n  = 9; divided into two groups) or SAH induction via endovascular perforation ( n  = 13, divided into two groups)...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28872734/xenon-as-an-adjuvant-to-sevoflurane-anesthesia-in-children-younger-than-4%C3%A2-years-of-age-undergoing-interventional-or-diagnostic-cardiac-catheterization-a-randomized-controlled-clinical-trial
#15
Sarah Devroe, Roselien Meeusen, Marc Gewillig, Bjorn Cools, Koen Poesen, Robert Sanders, Steffen Rex
BACKGROUND: Xenon has repeatedly been demonstrated to have only minimal hemodynamic side effects when compared to other anesthetics. Moreover, in experimental models, xenon was found to be neuroprotective and devoid of developmental neurotoxicity. These properties could render xenon attractive for the anesthesia in neonates and infants with congenital heart disease. However, experience with xenon anesthesia in children is scarce. AIMS: We hypothesized that in children undergoing cardiac catheterization, general anesthesia with a combination of sevoflurane with xenon results in superior hemodynamic stability, compared to sevoflurane alone...
December 2017: Paediatric Anaesthesia
https://www.readbyqxmd.com/read/28398653/the-noble-gas-xenon-provides-protection-and-trophic-stimulation-to-midbrain-dopamine-neurons
#16
Jérémie Lavaur, Déborah Le Nogue, Marc Lemaire, Jan Pype, Géraldine Farjot, Etienne C Hirsch, Patrick P Michel
Despite its low chemical reactivity, the noble gas xenon possesses a remarkable spectrum of biological effects. In particular, xenon is a strong neuroprotectant in preclinical models of hypoxic-ischemic brain injury. In this study, we wished to determine whether xenon retained its neuroprotective potential in experimental settings that model the progressive loss of midbrain dopamine (DA) neurons in Parkinson's disease. Using rat midbrain cultures, we established that xenon was partially protective for DA neurons through either direct or indirect effects on these neurons...
July 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28250763/molecular-chaperones-and-hypoxic-ischemic-encephalopathy
#17
REVIEW
Cong Hua, Wei-Na Ju, Hang Jin, Xin Sun, Gang Zhao
Hypoxic-ischemic encephalopathy (HIE) is a disease that occurs when the brain is subjected to hypoxia, resulting in neuronal death and neurological deficits, with a poor prognosis. The mechanisms underlying hypoxic-ischemic brain injury include excitatory amino acid release, cellular proteolysis, reactive oxygen species generation, nitric oxide synthesis, and inflammation. The molecular and cellular changes in HIE include protein misfolding, aggregation, and destruction of organelles. The apoptotic pathways activated by ischemia and hypoxia include the mitochondrial pathway, the extrinsic Fas receptor pathway, and the endoplasmic reticulum stress-induced pathway...
January 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28065636/neuroprotection-and-neurotoxicity-in-the-developing-brain-an-update-on-the-effects-of-dexmedetomidine-and-xenon
#18
REVIEW
Azeem Alam, Ka Chun Suen, Zac Hana, Robert D Sanders, Mervyn Maze, Daqing Ma
Growing and consistent preclinical evidence, combined with early clinical epidemiological observations, suggest potentially neurotoxic effects of commonly used anesthetic agents in the developing brain. This has prompted the FDA to issue a safety warning for all sedatives and anesthetics approved for use in children under three years of age. Recent studies have identified dexmedetomidine, the potent α2-adrenoceptor agonist, and xenon, the noble gas, as effective anesthetic adjuvants that are both less neurotoxic to the developing brain, and also possess neuroprotective properties in neonatal and other settings of acute ongoing neurologic injury...
March 2017: Neurotoxicology and Teratology
https://www.readbyqxmd.com/read/27830959/neonatal-hypoxic-ischemic-encephalopathy-an-update-on-disease-pathogenesis-and-treatment
#19
REVIEW
Edibe Pembegül Yıldız, Barış Ekici, Burak Tatlı
Hypoxic ischemic encephalopathy (HIE) is the most important reason for morbidity and mortality in term-born infants. Understanding pathophysiology of the brain damage is essential for the early detection of patients with high risk for HIE and development of strategies for their treatments. Areas covered: This review discusses pathophysiology of the neonatal HIE and its treatment options, including hypothermia, melatonin, allopurinol, topiramate, erythropoietin, N-acetylcyctein, magnesium sulphate and xenon...
May 2017: Expert Review of Neurotherapeutics
https://www.readbyqxmd.com/read/27689777/gas-chromatography-mass-spectrometry-measurement-of-xenon-in-gas-loaded-liposomes-for-neuroprotective-applications
#20
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 of Xe-ELIP lipid was infused intravenously into rats...
January 15, 2017: Rapid Communications in Mass Spectrometry: RCM
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