60 results found
Koziakova M, Harris K, Edge C, et al., 2019, Noble gas neuroprotection: Xenon and argon protect against hypoxic-ischaemic injury in rat hippocampus in vitro via distinct mechanisms, British Journal of Anaesthesia, Vol: 123, Pages: 601-609, ISSN: 1471-6771
BackgroundNoble gases may provide novel treatments for neurological injuries such as ischaemic and traumatic brain injury. Few studies have evaluated the complete series of noble gases under identical conditions in the same model.MethodsWe used an in vitro model of hypoxia–ischaemia to evaluate the neuroprotective properties of the series of noble gases, helium, neon, argon, krypton, and xenon. Organotypic hippocampal brain slices from mice were subjected to oxygen-glucose deprivation, and injury was quantified using propidium iodide fluorescence.ResultsBoth xenon and argon were equally effective neuroprotectants, with 0.5 atm of xenon or argon reducing injury by 96% (P<0.0001), whereas helium, neon, and krypton were devoid of any protective effect. Neuroprotection by xenon, but not argon, was reversed by elevated glycine.ConclusionsXenon and argon are equally effective as neuroprotectants against hypoxia–ischaemia in vitro, with both gases preventing injury development. Although xenon's neuroprotective effect may be mediated by inhibition of the N-methyl-d-aspartate receptor at the glycine site, argon acts via a different mechanism. These findings may have important implications for their clinical use as neuroprotectants.
Campos-Pires R, Mohamed-Ali N, Balaet M, et al., 2019, Xenon prevents early neuronal loss and neuroinflammation in a rat model of traumatic brain injury, BJA Research Forum / Anaesthetic Research Society, Publisher: Elsevier, Pages: e508-e509, ISSN: 0007-0912
Campos-Pires R, Yonis A, Pau A, et al., 2019, Delayed xenon treatment prevents injury development following blast-neurotrauma in vitro, 37th Annual National Neurotrauma Symposium, Publisher: Mary Ann Liebert, Pages: A40-A41, ISSN: 0897-7151
Campos-Pires R, Mohamed-Ali N, Balaet M, et al., 2019, XENON REDUCES SECONDARY INJURY, PREVENTS NEURONAL LOSS AND NEUROINFLAMMATION IN A RAT MODEL OF TRAUMATIC BRAIN INJURY, 37th Annual National Neurotrauma Symposium, Publisher: MARY ANN LIEBERT, INC, Pages: A116-A116, ISSN: 0897-7151
Campos-Pires R, Hirnet T, Valeo F, et al., 2019, XENON PREVENTS NEURODEGENERATION AND LATE-ONSET COGNITIVE IMPAIRMENT, AND IMPROVES SURVIVAL AFTER TRAUMATIC BRAIN INJURY IN MICE, 37th Annual National Neurotrauma Symposium, Publisher: MARY ANN LIEBERT, INC, Pages: A47-A47, ISSN: 0897-7151
Campos-Pires R, Hirnet T, Valeo F, et al., 2019, Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice, British Journal of Anaesthesia, Vol: 123, Pages: 60-73, ISSN: 0007-0912
Campos-Pires R, Mohamed-Ali N, Balaet M, et al., 2019, Xenon Treatment Reduces Secondary Injury Development and Prevents Neuronal Loss and Microglial Proliferation in a Rat Model of Traumatic Brain Injury, 13th World Conference on Brain injury, Pages: 222-222, ISSN: 0269-9052
Campos-Pires R, Yonis A, Pau A, et al., 2019, The Noble Gas Xenon Prevents Injury Development Following Blast-Traumatic Brain Injury In Vitro, 13th World Conference on Brain Injury, Pages: 218-218, ISSN: 0269-9052
Campos-Pires R, Hirnet T, Valeo F, et al., 2019, Xenon Treatment Prevents Late Onset Cognitive Impairment and Improves Survival Following Traumatic Brain Injury in Mice, 13th World Conference on Brain Injury, Pages: 220-220, ISSN: 0269-9052
Campos Pires R, Yonis A, Macdonald W, et al., 2018, A novel In vitro model of blast traumatic brain injury, Jove-Journal of Visualized Experiments, Vol: 142, ISSN: 1940-087X
Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the detonation of explosive devices, however, the mechanisms that underlie the brain damage resulting from blast overpressure exposure are not entirely understood and are believed to be unique to this type of brain injury. Preclinical models are crucial tools that contribute to better understand blast-induced brain injury. A novel in vitro blast TBI model was developed using an open-ended shock tube to simulate real-life open-field blast waves modelled by the Friedlander waveform. C57BL/6N mouse organotypic hippocampal slice cultures were exposed to single shock waves and the development of injury was characterized up to 72 h using propidium iodide, a well-established fluorescent marker of cell damage that only penetrates cells with compromised cellular membranes. Propidium iodide fluorescence was significantly higher in the slices exposed to a blast wave when compared with sham slices throughout the duration of the protocol. The brain tissue injury is very reproducible and proportional to the peak overpressure of the shock wave applied.
Campos-Pires R, Yonis A, Pau A, et al., 2018, Xenon is neuroprotective against blast traumatic brain injury in vitro, British Journal of Anaesthesia Research Forum, Publisher: Elsevier, Pages: e23-e23, ISSN: 0007-0912
Campos-Pires R, Armstrong S, Sebastiani A, et al., 2018, Xenon treatment improves short-term and long-term outcomes in a rodent model of traumatic brain injury, British Journal of Anaesthesia Research Forum, Publisher: Elsevier, Pages: e21-e21, ISSN: 0007-0912
Campos Pires R, Koziakova M, Yonis A, et al., 2018, Xenon protects against blast-induced traumatic brain injury in an in vitro model, Journal of Neurotrauma, Vol: 35, Pages: 1037-1044, ISSN: 0897-7151
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. Exposure to blast shockwave resulted in significant (p < 0.01) injury that increased with peak-overpressure and impulse of the shockwave, and which exhibited a secondary injury development up to 72 h after trauma. Blast-induced propidium iodide fluorescence overlapped with cleaved caspase-3 immunofluorescence, indicating that shock-wave–induced cell death involves apoptosis. Xenon (50% atm) applied 1 h after blast exposure reduced injury 24 h (p < 0.01), 48 h (p < 0.05), and 72 h (p < 0.001) later, compared with untreated control injury. Xenon-treated injured slices were not significantly different from uninjured sham slices at 24 h and 72 h. We demonstrate for the first time that xenon treatment after blast traumatic brain injury reduces initial injury and prevents subsequent injury development in vitro. Our findings support the idea that xenon may be a potential first-line treatment for those with blast-induced traumatic brain injury.
Baroness Finlay of Llandaff I, Myers I, Dickinson R, et al., 2017, Carbon Monoxide Poisoning: Saving Lives, Advancing Treatment, Carbon Monoxide Poisoning: Saving Lives, Advancing Treatment, London, Publisher: All Party Parliamentary Group on Carbon Monoxide
Carbon monoxide (CO) poisoning is a serious public health issue. In England and Wales alone, every year some 4,000 attendances to emergency departments (EDs) are the result of accidental CO poisoning. Statistics show that CO kills more than 30 people a year and leads to around 200 hospital admissions, but these figures are likely to be a gross underestimate. Consequently, treating accidental CO poisoning may actually be costing much more than the estimated £178 million per annum.Healthcare professionals have a vital role to play in preventing, diagnosing and treating patients exposed to CO. However, these professionals face a number of barriers to action: gaps in knowledge, limited awareness, and a lack of co-ordination within and between the healthcare sectors. These barriers need to be removed if we are to reduce significantly the number of accidental deaths and unnecessary injuries caused by CO poisoning, and to improve patient management and recovery.This report has been prepared by members of COMed, the healthcare professionals’ sub-group of the APPCOG Stakeholder Forum. It presents a number of hard-hitting essays that review current knowledge and practice on the diagnosis and management of CO poisoning in the healthcare system. It identifies gaps in knowledge and practice, and makes recommendations to close those gaps so that diagnosis, patient management and recovery can be improved.The findings presented in this report led members of the sub-group to conclude that:A lack of awareness amongst healthcare professionals of CO poisoning as a cause of illness is very likely to be impacting adversely on public health outcomes. Much remains to be discovered and explained about the link between low level chronic CO exposure and long-term effects on an individual’s health - for example, its impact on diseases of the cardiovascular and neurological system and whether CO is a casual factor of disease or involved in disease processes not previously
Campos-Pires R, Edge CJ, Dickinson R, 2016, Argon: A Noble Foe for Subarachnoid Hemorrhage, Critical Care Medicine, Vol: 44, Pages: 1456-1457, ISSN: 1530-0293
Campos-Pires R, Armstrong SP, Sebastiani A, et al., 2016, THE NOBLE GAS XENON REDUCES SECONDARY INJURYAND IMPROVES LONG-TERM LOCOMOTOR FUNCTION AFTER TRAUMATIC BRAIN INJURY IN RODENTS, 27th International Symposium on Cerebral Blood Flow, Metabolism and Function / 12th International Conference on Quantification of Brain Function with PET, Publisher: SAGE PUBLICATIONS INC, Pages: 308-309, ISSN: 0271-678X
Campos-Pires R, Armstrong S, Sebastiani A, et al., 2016, Xenon provides short-term and long-term neuroprotection in a rodent model of traumatic brain injury, International Brain Injury Association’s Eleventh World Congress on Brain Injury, Publisher: Taylor & Francis, Pages: 653-653, ISSN: 1362-301X
Harris K, Armstrong S, Campos-Pires R, et al., 2016, Neuroprotection against traumatic brain injury by xenon, but not argon, is mediated by inhibition at the N-methyl-D-aspartate receptor glycine site, International Brain Injury Association’s Eleventh World Congress on Brain Injury, Publisher: Taylor & Francis, Pages: 606-606, ISSN: 1362-301X
Campos-Pires R, Dickinson R, 2016, Modelling Blast Brain Injury, Blast Injury Science and Engineering A Guide for Clinicians and Researchers, Editors: Clasper, Bull, Mahoney, Publisher: Springer, Pages: 173-182, ISBN: 9783319218670
The consequences of blast traumatic brain injury (blast-TBI) in humans are largely determined by the characteristics of the trauma insult and, within certain limits, the individual responses to the lesions inflicted (1). In blast-TBI the mechanisms of brain vulnerability to the detonation of an explosive device are not entirely understood. They most likely result from a combination of the different physical aspects of the blast phenomenon, specifically extreme pressure oscillations (blast-overpressure wave), projectile penetrating fragments and acceleration-deceleration forces, creating a spectrum of brain injury that ranges from mild to severe blast-TBI (2). The pathophysiology of penetrating and inertially-driven blast-TBI has been extensively investigated for many years. However, the brain damage caused by blast-overpressure is much less understood and is unique to this type of TBI (3). Indeed, there continues to be debate about how the pressure wave is transmitted and reflected through the brain and how it causes cellular damage (4). No single model can mimic the clinical and mechanical complexity resulting from a real life blast-TBI (3). The different models, non-biological (in silico or surrogate physical) and biological (ex vivo, in vitro or in vivo), tend to complement each other.
Campos-Pires R, Armstrong S, Sebastiani A, et al., 2015, Xenon provides short term & long term neuroprotection in an in vivo model of traumatic brain injury., BNA Festival of Neuroscience, Pages: 1-1
Koziakova M, Harris K, Campos-Pires R, et al., 2015, The neuroprotective efficacy of noble gases in an in vitro model of ischemic brain injury., British Neuroscience Association, Publisher: BNA
Campos-Pires R, Sebastiani A, Hirnet T, et al., 2015, Xenon provides short term & long term neuroprotection in an in vivo model of traumatic brain injury, British Neuroscience Associaton
Campos-Pires R, Armstrong SP, Sebastiani A, et al., 2015, Xenon Improves Neurologic Outcome and Reduces Secondary Injury Following Trauma in an In Vivo Model of Traumatic Brain Injury, Critical Care Medicine, Vol: 43, Pages: 149-158, ISSN: 1530-0293
Objectives: To determine the neuroprotective efficacy of the inert gas xenon following traumatic brain injury and to determine whether application of xenon has a clinically relevant therapeutic time window.Design: Controlled animal study.Setting: University research laboratory.Subjects: Male C57BL/6N mice (n = 196).Interventions: Seventy-five percent xenon, 50% xenon, or 30% xenon, with 25% oxygen (balance nitrogen) treatment following mechanical brain lesion by controlled cortical impact.Measurements and Main Results: Outcome following trauma was measured using 1) functional neurologic outcome score, 2) histological measurement of contusion volume, and 3) analysis of locomotor function and gait. Our study shows that xenon treatment improves outcome following traumatic brain injury. Neurologic outcome scores were significantly (p < 0.05) better in xenon-treated groups in the early phase (24 hr) and up to 4 days after injury. Contusion volume was significantly (p < 0.05) reduced in the xenon-treated groups. Xenon treatment significantly (p < 0.05) reduced contusion volume when xenon was given 15 minutes after injury or when treatment was delayed 1 or 3 hours after injury. Neurologic outcome was significantly (p < 0.05) improved when xenon treatment was given 15 minutes or 1 hour after injury. Improvements in locomotor function (p < 0.05) were observed in the xenon-treated group, 1 month after trauma.Conclusions: These results show for the first time that xenon improves neurologic outcome and reduces contusion volume following traumatic brain injury in mice. In this model, xenon application has a therapeutic time window of up to at least 3 hours. These findings support the idea that xenon may be of benefit as a neuroprotective treatment in patients with brain trauma.
Bertaccini EJ, Dickinson R, Trudell JR, et al., 2014, Molecular modeling of a tandem two pore domain potassium channel reveals a putative binding Site for general anesthetics, ACS Chemical Neuroscience, Vol: 5, Pages: 1246-1252, ISSN: 1948-7193
Anesthetics are thought to mediate a portion of their activity via binding to and modulation of potassium channels. In particular, tandem pore potassium channels (K2P) are transmembrane ion channels whose current is modulated by the presence of general anesthetics and whose genetic absence has been shown to confer a level of anesthetic resistance. While the exact molecular structure of all K2P forms remains unknown, significant progress has been made toward understanding their structure and interactions with anesthetics via the methods of molecular modeling, coupled with the recently released higher resolution structures of homologous potassium channels to act as templates. Such models reveal the convergence of amino acid regions that are known to modulate anesthetic activity onto a common three- dimensional cavity that forms a putative anesthetic binding site. The model successfully predicts additional important residues that are also involved in the putative binding site as validated by the results of suggested experimental mutations. Such a model can now be used to further predict other amino acid residues that may be intimately involved in the target-based structure–activity relationships that are necessary for anesthetic binding.
Harris K, Armstrong SP, Campos-Pires R, et al., 2013, Neuroprotection against traumatic brain injury by xenon but not argon, is mediated by inhibition at the NMDA receptor glycine site, Anesthesiology, Vol: 119, Pages: 1137-1148, ISSN: 1528-1175
Background. The inert anesthetic gas xenon is neuroprotective in models of brain injury. Weinvestigate the neuroprotective mechanisms of the inert gases xenon, argon, krypton, neon andhelium in an in vitro model of traumatic brain injury.Methods. We use an in vitro model using mouse organotypic hippocampal brain-slices, subjectedto a focal mechanical trauma, with injury quantified by propidium-iodide fluorescence. Patch-clampelectrophysiology is used to investigate the effect of the inert gases on N-methyl-D-aspartate(NMDA)-receptors and TREK-1 channels, two molecular targets likely to play a role inneuroprotection.Results. Xenon(50%) and, to a lesser extent, argon(50%) are neuroprotective against traumaticinjury when applied following injury [xenon 43±1% protection 72hours after injury (N=104); argon30±6% protection (N=44); mean±SEM]. Helium, neon and krypton are devoid of neuroprotectiveeffect. Xenon(50%) prevents development of secondary injury up to 48 hours after trauma.Argon(50%) attenuates secondary injury, but is less effective than xenon [xenon 50±5% reductionin secondary injury 72hours after injury (N=104); argon 34±8% reduction (N=44); mean±SEM].Glycine reverses the neuroprotective effect of xenon, but not argon, consistent with competitiveinhibition at the NMDA receptor glycine-site mediating xenon neuroprotection against traumaticbrain injury. Xenon inhibits NMDA receptors and activates TREK-1 channels, while argon,krypton, neon and helium have no effect on these ion-channels.Conclusions. Xenon neuroprotection against traumatic brain injury can be reversed by elevatingthe glycine concentration, consistent with inhibition at the NMDA-receptor glycine site playing asignificant role in xenon neuroprotection. Argon and xenon do not act via the same mechanism.
Yip GMS, Chen Z-W, Edge CJ, et al., 2013, A propofol binding site on mammalian GABA(A) receptors identified by photolabeling (vol 9, pg 715, 2013), NATURE CHEMICAL BIOLOGY, Vol: 9, ISSN: 1552-4450
Yip GM, Chen ZW, Edge CJ, et al., 2013, A propofol binding site on mammalian GABAA receptors identified by photolabeling, Nature Chemical Biology, Vol: 9, Pages: 715-720, ISSN: 1552-4469
Propofol is the most important intravenous general anesthetic in current clinical use. It acts by potentiating GABAA (γ-aminobutyric acid type A) receptors, but where it binds to this receptor is not known and has been a matter of some debate. We synthesized a new propofol analog photolabeling reagent whose biological activity is very similar to that of propofol. We confirmed that this reagent labeled known propofol binding sites in human serum albumin that have been identified using X-ray crystallography. Using a combination of protiated and deuterated versions of the reagent to label mammalian receptors in intact membranes, we identified a new binding site for propofol in GABAA receptors consisting of both β3 homopentamers and α1β3 heteropentamers. The binding site is located within the β subunit at the interface between the transmembrane domains and the extracellular domain and lies close to known determinants of anesthetic sensitivity in the transmembrane segments TM1 and TM2.
Harris K, Campos-Pires R, Kiru L, et al., 2013, The NMDA receptor glycine site mediates xenon neuroprotection against traumatic brain injury in vitro, British Neuroscience Association Meeting
Geldart CH, McKitrick TJW, Armstrong SP, et al., 2012, Identification of two mutations (F758W & F758Y) in the N-Methyl-D-Aspartate receptor glycine-binding site that selectively prevent competitive inhibition by xenon without affecting glycine binding, Anaesthetic Research Society Meeting, London
Geldart CH, McKitrick TJW, Armstrong SP, et al., 2012, Identification of two mutations (F758W & F758Y) in the N-Methyl-D-Aspartate receptor glycine-binding site that selectively prevent competitive inhibition by xenon without affecting glycine binding, Anaesthetic Reasearch Society Meeting
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.