Zusammenfassung
Edelgase sind chemisch inerte Elemente, die z. T. biologische Aktivität haben. Besonders neuroprotektive Eigenschaften sind für Xenon, Argon und auch Helium experimentell gut belegt. Die zugrunde liegenden Mechanismen hierfür sind noch nicht vollständig aufgeklärt. Neben der Beeinflussung von neuronalen Ionenkanälen und zellulären Signaltransduktionskaskaden sowie antiapoptotischen Effekten scheint auch die Modulation der Neuroinflammation eine entscheidende Rolle zu spielen. Die vorliegende Übersicht beleuchtet den aktuellen Stand der Forschung zur Neuroprotektion durch Edelgase mit einem Fokus auf Interaktionen mit dem neuronal-glialen Netzwerk sowie der Neuroinflammation und gibt einen Ausblick auf mögliche klinische Anwendungen.
Abstract
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.
Literatur
Arola OJ, Laitio RM, Roine RO, Gronlund J, Saraste A, Pietila M et al (2013) Feasibility and cardiac safety of inhaled xenon in combination with therapeutic hypothermia following out-of-hospital cardiac arrest. Crit Care Med 41:2116–2124
Banks P, Franks NP, Dickinson R (2010) Competitive inhibition at the glycine site of the N-methyl-D-aspartate receptor mediates xenon neuroprotection against hypoxia-ischemia. Anesthesiology 112:614–622
Bantel C, Maze M, Trapp S (2009) Neuronal preconditioning by inhalational anesthetics: evidence for the role of plasmalemmal adenosine triphosphate-sensitive potassium channels. Anesthesiology 110:986–995
Bantel C, Maze M, Trapp S (2010) Noble gas xenon is a novel adenosine triphosphate-sensitive potassium channel opener. Anesthesiology 112:623–630
Brucken A, Cizen A, Fera C, Meinhardt A, Weis J, Nolte K et al (2013) Argon reduces neurohistopathological damage and preserves functional recovery after cardiac arrest in rats. Br J Anaesth 110(Suppl 1):i106–i112
Brucken A, Kurnaz P, Bleilevens C, Derwall M, Weis J, Nolte K et al (2014) Dose dependent neuroprotection of the noble gas argon after cardiac arrest in rats is not mediated by K-Channel opening. Resuscitation 85:826–832
Cattano D, Valleggi S, Ma D, Kastsiuchenka O, Abramo A, Sun P et al (2008) Xenon induces transcription of ADNP in neonatal rat brain. Neurosci Lett 440:217–221
Chakkarapani E, Dingley J, Liu X, Hoque N, Aquilina K, Porter H et al (2010) Xenon enhances hypothermic neuroprotection in asphyxiated newborn pigs. Ann Neurol 68:330–341
Coburn M, Maze M, Franks NP (2008) The neuroprotective effects of xenon and helium in an in vitro model of traumatic brain injury. Crit Care Med 36:588–595
Coburn M, Sanders RD, Maze M, Rossaint R (2012) The Hip Fracture Surgery in Elderly Patients (HIPELD) study: protocol for a randomized, multicenter controlled trial evaluating the effect of xenon on postoperative delirium in older patients undergoing hip fracture surgery. Trials 13:180
David HN, Haelewyn B, Chazalviel L, Lecocq M, Degoulet M, Risso JJ et al (2009) Post-ischemic helium provides neuroprotection in rats subjected to middle cerebral artery occlusion-induced ischemia by producing hypothermia. J Cereb Blood Flow Metab 29:1159–1165
David HN, Haelewyn B, Degoulet M, Colomb DG Jr, Risso JJ, Abraini JH (2012) Ex vivo and in vivo neuroprotection induced by argon when given after an excitotoxic or ischemic insult. PLoS One 7:e30934
Dingley J, Tooley J, Liu X, Scull-Brown E, Elstad M, Chakkarapani E et al (2014) Xenon ventilation during therapeutic hypothermia in neonatal encephalopathy: a feasibility study. Pediatrics 133:809–818 (PMID:24777219)
Dingley J, Tooley J, Porter H, Thoresen M (2006) Xenon provides short-term neuroprotection in neonatal rats when administered after hypoxia-ischemia. Stroke 37:501–506
Dinse A, Fohr KJ, Georgieff M, Beyer C, Bulling A, Weigt HU (2005) Xenon reduces glutamate-, AMPA-, and kainate-induced membrane currents in cortical neurones. Br J Anaesth 94:479–485
Fahlenkamp AV, Coburn M, de Prada A, Gereitzig N, Beyer C, Haase H et al (2014) Expression analysis following argon treatment in an in vivo model of transient middle cerebral artery occlusion in rats. Med Gas Res 4:11. doi:10.1186/2045-9912-4-11. eCollection;%2014.:11–14
Fahlenkamp AV, Coburn M, Haase H, Kipp M, Ryang YM, Rossaint R et al (2011) Xenon enhances LPS-induced IL-1beta expression in microglia via the extracellular signal-regulated kinase 1/2 pathway. J Mol Neurosci 45:48–59
Fahlenkamp AV, Rossaint R, Haase H, Al Kassam H, Ryang YM, Beyer C et al (2012) The noble gas argon modifies extracellular signal-regulated kinase 1/2 signaling in neurons and glial cells. Eur J Pharmacol 674:104–111
Faulkner S, Bainbridge A, Kato T, Chandrasekaran M, Kapetanakis AB, Hristova M et al (2011) Xenon augmented hypothermia reduces early lactate/N-acetylaspartate and cell death in perinatal asphyxia. Ann Neurol 70:133–150
Finnie JW (2013) Neuroinflammation: beneficial and detrimental effects after traumatic brain injury. Inflammopharmacology 21:309–320
Franks NP, Dickinson R, de Sousa SL, Hall AC, Lieb WR (1998) How does xenon produce anaesthesia? Nature 396:324
Fries M, Brucken A, Cizen A, Westerkamp M, Lower C, Deike-Glindemann J et al (2012) Combining xenon and mild therapeutic hypothermia preserves neurological function after prolonged cardiac arrest in pigs. Crit Care Med 40:1297–1303
Fries M, Nolte KW, Coburn M, Rex S, Timper A, Kottmann K et al (2008) Xenon reduces neurohistopathological damage and improves the early neurological deficit after cardiac arrest in pigs. Crit Care Med 36:2420–2426
Gruss M, Bushell TJ, Bright DP, Lieb WR, Mathie A, Franks NP (2004) Two-pore-domain K + channels are a novel target for the anesthetic gases xenon, nitrous oxide, and cyclopropane. Mol Pharmacol 65:443–452
Harris K, Armstrong SP, Campos-Pires R, Kiru L, Franks NP, Dickinson R (2013) Neuroprotection against traumatic brain injury by xenon, but not argon, is mediated by inhibition at the N-methyl-D-aspartate receptor glycine site. Anesthesiology 119:1137–1148
Hernandez-Ontiveros DG, Tajiri N, Acosta S, Giunta B, Tan J, Borlongan CV (2013) Microglia activation as a biomarker for traumatic brain injury. Front Neurol 4:30. doi:10.3389/fneur.2013.00030. eCollection;%2013.:30
Hobbs C, Thoresen M, Tucker A, Aquilina K, Chakkarapani E, Dingley J (2008) Xenon and hypothermia combine additively, offering long-term functional and histopathologic neuroprotection after neonatal hypoxia/ischemia. Stroke 39:1307–1313
Hollig A, Schug A, Fahlenkamp AV, Rossaint R, Coburn M (2014) Argon: systematic review on neuro- and organoprotective properties of an „inert“ gas. Int J Mol Sci 15:18175–18196
Jawad N, Rizvi M, Gu J, Adeyi O, Tao G, Maze M et al (2009) Neuroprotection (and lack of neuroprotection) afforded by a series of noble gases in an in vitro model of neuronal injury. Neurosci Lett 460:232–236
Koblin DD, Fang Z, Eger EI, Laster MJ, Gong D, Ionescu P et al (1998) Minimum alveolar concentrations of noble gases, nitrogen, and sulfur hexafluoride in rats: helium and neon as nonimmobilizers (nonanesthetics). Anesth Analg 87:419–424
Kumar A, Loane DJ (2012) Neuroinflammation after traumatic brain injury: opportunities for therapeutic intervention. Brain Behav Immun 26:1191–1201
Liu Y, Xue F, Liu G, Shi X, Liu Y, Liu W et al (2011) Helium preconditioning attenuates hypoxia/ischemia-induced injury in the developing brain. Brain Res 1376:122–129. doi:10.1016/j.brainres.2010.12.068 (2010 Dec 29.:122–129)
Loetscher PD, Rossaint J, Rossaint R, Weis J, Fries M, Fahlenkamp A et al (2009) Argon: neuroprotection in in vitro models of cerebral ischemia and traumatic brain injury. Crit Care 13:R206
Luo Y, Ma D, Ieong E, Sanders RD, Yu B, Hossain M et al (2008) Xenon and sevoflurane protect against brain injury in a neonatal asphyxia model. Anesthesiology 109:782–789
Ma D, Hossain M, Chow A, Arshad M, Battson RM, Sanders RD et al (2005) Xenon and hypothermia combine to provide neuroprotection from neonatal asphyxia. Ann Neurol 58:182–193
Ma D, Hossain M, Pettet GK, Luo Y, Lim T, Akimov S et al (2006) Xenon preconditioning reduces brain damage from neonatal asphyxia in rats. J Cereb Blood Flow Metab 26:199–208
Murray PJ, Smale ST (2012) Restraint of inflammatory signaling by interdependent strata of negative regulatory pathways. Nat Immunol 13:916–924
Natale G, Cattano D, Abramo A, Forfori F, Fulceri F, Fornai F et al (2006) Morphological evidence that xenon neuroprotects against N-methyl-DL-aspartic acid-induced damage in the rat arcuate nucleus: a time-dependent study. Ann N Y Acad Sci 1074:650–658
Pan Y, Zhang H, Acharya AB, Cruz-Flores S, Panneton WM (2011) The effect of heliox treatment in a rat model of focal transient cerebral ischemia. Neurosci Lett 497:144–147
Pan Y, Zhang H, VanDeripe DR, Cruz-Flores S, Panneton WM (2007) Heliox and oxygen reduce infarct volume in a rat model of focal ischemia. Exp Neurol 205:587–590
Petzelt C, Blom P, Schmehl W, Muller J, Kox WJ (2003) Prevention of neurotoxicity in hypoxic cortical neurons by the noble gas xenon. Life Sci 72:1909–1918
Ristagno G, Fumagalli F, Russo I, Tantillo S, Zani DD, Locatelli V et al (2014) Postresuscitation treatment with argon improves early neurological recovery in a porcine model of cardiac arrest. Shock 41:72–78
Ryang YM, Fahlenkamp AV, Rossaint R, Wesp D, Loetscher PD, Beyer C et al (2011) Neuroprotective effects of argon in an in vivo model of transient middle cerebral artery occlusion in rats. Crit Care Med 39:1448–1453
Sabir H, Bishop S, Cohen N, Maes E, Liu X, Dingley J et al (2013) Neither xenon nor fentanyl induces neuroapoptosis in the newborn pig brain. Anesthesiology 119:345–357
Sheng SP, Lei B, James ML, Lascola CD, Venkatraman TN, Jung JY et al (2012) Xenon neuroprotection in experimental stroke: interactions with hypothermia and intracerebral hemorrhage. Anesthesiology 117:1262–1275
Ulbrich F, Kaufmann KB, Coburn M, Lagreze WA, Roesslein M, Biermann J et al (2015) Neuroprotective effects of Argon are mediated via an ERK-1/2 dependent regulation of heme-oxygenase-1 in retinal ganglion cells. J Neurochem 134:717–727
Ulbrich F, Schallner N, Coburn M, Loop T, Lagreze WA, Biermann J et al (2014) Argon inhalation attenuates retinal apoptosis after ischemia/reperfusion injury in a time- and dose-dependent manner in rats. PLoS One 9:e115984
Yang YW, Cheng WP, Lu JK, Dong XH, Wang CB, Zhang J et al (2014) Timing of xenon-induced delayed postconditioning to protect against spinal cord ischaemia-reperfusion injury in rats. Br J Anaesth 113:168–176
Yang YW, Lu JK, Qing EM, Dong XH, Wang CB, Zhang J et al (2012) Post-conditioning by xenon reduces ischaemia-reperfusion injury of the spinal cord in rats. Acta Anaesthesiol Scand 56:1325–1331
Zhuang L, Yang T, Zhao H, Fidalgo AR, Vizcaychipi MP, Sanders RD et al (2012) The protective profile of argon, helium, and xenon in a model of neonatal asphyxia in rats. Crit Care Med 40:1724–1730
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Interessenkonflikt
A.V. Fahlenkamp hat eine Reisekostenübernahme zu einem Studienprüfer-Treffen von Air Liquide Sante International, einem Unternehmen das medizinische Gase wie Xenon und Argon vertreibt, erhalten. R. Rossaint und M. Coburn haben Beratungstätigkeiten vergütet, Studienunterstützungen sowie Honorare für Vorträge von Air Liquide Sante International bekommen.
Dieser Beitrag beinhaltet keine Studien an Menschen oder Tieren.
Additional information
A.V. Fahlenkamp ist Mitglied des „Wissenschaftlichen Arbeitskreises Wissenschaftlicher Nachwuchs (WAKWiN)“ der Deutschen Gesellschaft für Anästhesiologie und Intensivmedizin e. V. (DGAI).
Rights and permissions
About this article
Cite this article
Fahlenkamp, A., Rossaint, R. & Coburn, M. Neuroprotektion durch Edelgase. Anaesthesist 64, 855–858 (2015). https://doi.org/10.1007/s00101-015-0079-6
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00101-015-0079-6