rmtОбщая реаниматологияGeneral Reanimatology1813-97792411-7110FSBI "SRIGR" RAMS10.15360/1813-9779-2023-3-46-53rmt-2312Research ArticleЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯEXPERIMENTAL STUDIESИзучение нейропротективного эффекта ингаляции аргон-кислородной смеси после фотоиндуцированного ишемического инсультаExperimental Study of Neuroprotective Properties of Inhaled Argon-Oxygen Mixture in a Photoinduced Ischemic Stroke ModelБоеваЕ. А.BoevaE. A.

Екатерина Александровна Боева, ведущий научный сотрудник

 Россия, 107031, г. Москва, ул. Петровка, д. 25, стр. 2 

 

 Ekatherine A. Boeva 

 25 Petrovka Str., Bldg. 2, 107031 Moscow, Russia 

eboeva@fnkcrr.ruСилачевД. Н.SilachevD. N.

Денис Николаевич Силачев

 Россия, 119992, г. Москва, ул. Ленинские Горы, д. 1 стр. 40 

 Denis N. Silachev 

 1 Leninskie gory, Bldg 40, 119992 Moscow, Russia 

proteins@mail.ruЯкуповаЭ. И.YakupovaE. I.

Эльмира Якупова

 Россия, 119992, г. Москва, ул. Ленинские Горы, д. 1 стр. 40 

 Elmira I. Yakupova 

 1 Leninskie gory, Bldg 40, 119992 Moscow, Russia 

elmira.yaku@gmail.comМиловановаМ. А.MilovanovaM. A.

Марина Алексеевна Милованова

Россия, 107031, г. Москва, ул. Петровка, д. 25, стр. 2 

 Marina A. Milovanova 

 25 Petrovka Str., Bldg. 2, 107031 Moscow, Russia 

mmilovanova@fnkcrr.ruВарнаковаЛ. А.VarnakovaL. A.

 Россия, 107031, г. Москва, ул. Петровка, д. 25, стр. 2 

 Lydia A. Varnakova 

 25 Petrovka Str., Bldg. 2, 107031 Moscow, Russia 

lvarnakova@fnkcrr.ruКалабушевС. Н.KalabushevS. N.

 Россия, 107031, г. Москва, ул. Петровка, д. 25, стр. 2 

 Sergey N. Kalabushev 

 25 Petrovka Str., Bldg. 2, 107031 Moscow, Russia 

skalabushev@fnkcrr.ruДенисовС. О.DenisovS. O.

Сергей Олегович Денисов

 Россия, 107031, г. Москва, ул. Петровка, д. 25, стр. 2 

 Sergey O. Denisov 

 25 Petrovka Str., Bldg. 2, 107031 Moscow, Russia 

sdenisov@fnkcrr.ruАнтоноваВ. В.AntonovaV. V.

 Россия, 107031, г. Москва, ул. Петровка, д. 25, стр. 2 

 Victoria V. Antonova 

 25 Petrovka Str., Bldg. 2, 107031 Moscow, Russia 

vantonova@fnkcrr.ruРыжковИ. А.RyzhkovI. A.

 Россия, 107031, г. Москва, ул. Петровка, д. 25, стр. 2 

 Ivan A. Ryzhkov 

 25 Petrovka Str., Bldg. 2, 107031 Moscow, Russia 

iryzhkov@fnkcrr.ruЛапинК. Н.LapinK. N.

 Россия, 107031, г. Москва, ул. Петровка, д. 25, стр. 2 

 Konstantin N. Lapin 

 25 Petrovka Str., Bldg. 2, 107031 Moscow, Russia 

klapin@fnkcrr.ruГребенчиковаА. А.GrebenchikovaA. A.

 Россия, 127473, г. Москва, ул. Делегатская, д. 20, стр. 1 

 Alexandra A. Grebenchikova 

20 Delegatskaya Str., Build 1, 127473 Moscow, Russia 

ogrebenchikov@fnkcrr.ruНИИ общей реаниматологии им. В. А. Неговского Федерального научно-клинического центра реаниматологии и реабилитологииРоссияV. A. Negovsky Research Institute of General Reanimatology, Federal Research and Clinical Center of Intensive Care Medicine and RehabilitologyRussian FederationНИИ Физико-химической биологии им. А. Н. Белозерского, Московский государственный университет им. М. В. ЛомоносоваРоссияA.N. Belozersky Research Institute of Physical and Chemical Biology, M. V. Lomonosov Moscow State UniversityRussian FederationМосковский государственный медико-стоматологический университет им. А. И. Евдокимова Минздрава РоссииРоссияA.I. Evdokimov Moscow State University of medicine and dentistry, Ministry of Health of RussiaRussian Federation2023230620231934653Copyright © Боева Е.А., Силачев Д.Н., Якупова Э.И., Милованова М.А., Варнакова Л.А., Калабушев С.Н., Денисов С.О., Антонова В.В., Рыжков И.А., Лапин К.Н., Гребенчикова А.А., 20232023Боева Е.А., Силачев Д.Н., Якупова Э.И., Милованова М.А., Варнакова Л.А., Калабушев С.Н., Денисов С.О., Антонова В.В., Рыжков И.А., Лапин К.Н., Гребенчикова А.А.Boeva E.A., Silachev D.N., Yakupova E.I., Milovanova M.A., Varnakova L.A., Kalabushev S.N., Denisov S.O., Antonova V.V., Ryzhkov I.A., Lapin K.N., Grebenchikova A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.reanimatology.com/rmt/article/view/2312

Острый ишемический инсульт является серьезной проблемой здравоохранения во всем мире. Поиск оптимального нейропротектора — важная задача. Во многих исследованиях было продемонстрировано, что аргон обладает нейропротективными свойствами при ишемическом повреждении головного мозга. Однако, данные таких исследований противоречивы.Цель исследования. Оценить влияние 24-часовой ингаляции аргон-кислородной смеси (Ar 70%/O₂ 30%) после фотоиндуцированного ишемического инсульта на выраженность неврологического дефицита и степень повреждения головного мозга у крыс.Материал и методы. Эксперименты провели на крысах-самцах линии Wistar весом 430–530 г (n=26). Фокальный ишемический инсульт моделировали в сенсомоторной коре головного мозга крыс с помощью фотохимически индуцированного сосудистого тромбоза. Животных случайным образом разделили на 3 группы: ложно-оперированные животные + ингаляция N₂ 70%/O₂ 30% (ЛО, n=6); Инсульт + ингаляция N₂ 70%/O₂ 30% (Инсульт, n=10); Инсульт + ингаляция Ar 70%/O₂ 30% (Инсульт+iAr, n=10). Неврологический статус оценивали в течение 14 дней в тесте «Постановка конечности на опору (ПКО)». Также через 14 сут после инсульта выполнили магнитно-резонансную томографию (МРТ) головного мозга с морфометрической оценкой размера очага повреждения. При оценке на 3-и, 7-е и 14-е сут сумма баллов теста ПКО в группах Инсульт и Инсульт+iAr была меньше, чем в группе ЛО.Результаты. Получили статистически значимые по результатам ПКО теста различия между группами ЛО, Инсульт и Инсульт + iAr на 3-е сут (14 (13; 14), 6,5 (4; 8), 5 (3; 8), p=0,027). Однако относительно друг друга группы Инсульт и Инсульт + iAr не отличались.Заключение. 24-часовая ингаляция аргон-кислородной смеси (Ar 70%/O₂ 30%) после инсульта не уменьшает объем повреждения головного мозга и не снижает выраженность неврологического дефицита.

Acute ischemic stroke is a serious problem for healthcare systems worldwide. Searching for the optimal neuroprotector is a contemporary challenge. Various studies have demonstrated neuroprotective properties of argon in ischemic brain damage models. However, the published data are inconsistent.The aim of the study was to evaluate the effect of 24-hour argon-oxygen mixture (Ar 70%/O₂ 30%) inhalation on the severity of neurological deficit and the extent of brain damage in rats after a photoinduced ischemic stroke. Material and methods. The experiments were carried out on male Wistar rats weighing 430–530 g (N=26). Focal ischemic stroke was modeled in the sensorimotor cortex of the rat brain using photochemically induced vascular thrombosis. The animals were randomly divided into 3 groups: sham procedure + N₂ 70%/O₂ 30% inhalation (SP, N=6); stroke + N₂ 70%/O₂ 30% inhalation (Stroke, N=10); Stroke + Ar 70%/O₂ 30% inhalation (Stroke+iAr, N=10). The limb placement test (LPT) was used for neurological assessment during 14 days. Additionally, on day 14 after the stroke, brain MRI with lesion size morphometry was performed. Summarized for days 3,7 and 14 LPT scores were lower in the Stroke and Stroke + iAr groups as compared to the SP group.Results. Statistically significant differences in LPT scores between SP, Stroke, and Stroke+iAr groups were revealed on day 3 post-stroke: (scores: 14 (13; 14), 6.5 (4; 8), and 5 (3; 8), respectively, P=0.027). However, there was no statistical difference between the Stroke and Stroke+iAr groups.Conclusion. 24-hour inhalation of argon-oxygen mixture (Ar 70%/O₂ 30%) after stroke does not reduce the extent of brain damage or the severity of neurological deficit.

аргоннейропротекцияфотоиндуцированный ишемический инсульторганопротекцияargonneuroprotectionphotochemically induced ischemic strokeorganoprotectionReferencesJurcau A., Simion A. Neuroinflammation in cerebral ischemia and ischemia/reperfusion injuries: from pathophysiology to therapeutic strategies. Int J Mol Sci. 2021; 23 (1): 14. DOI: 10.3390/ijms23010014. PMID: 35008440.Jurcau A., Simion A. Neuroinflammation in cerebral ischemia and ischemia/reperfusion injuries: from pathophysiology to therapeutic strategies. Int J Mol Sci. 2021; 23 (1): 14. DOI: 10.3390/ijms23010014. PMID: 35008440.Черпаков Р.А., Гребенчиков О.А. Влияние концентрации хлорида лития на его нейропротекторные свойства при ишемическом инсульте у крыс. Общая реаниматология. 2021; 17 (5): 101–110. DOI: 10.15360/1813-9779-2021-5-101-110Cherpakov R.A., Grebenchikov O.A. Effect of lithium chloride concentration on its neuroprotective properties in ischemic stroke in rats. General Reanimatology /Obshchaya Reanimatologiya. 2021; 17 (5): 101–110. (In Russ.). DOI: 10.15360/1813-9779-2021-5-101-110Paul S., Candelario-Jalil E. Emerging neuroprotective strategies for the treatment of ischemic stroke: an overview of clinical and preclinical studies. Exp Neurol. 2021; 335: 113518. doi: 10.1016/j.expneurol.2020.113518. PMID: 33144066Paul S., Candelario-Jalil E. Emerging neuroprotective strategies for the treatment of ischemic stroke: an overview of clinical and preclinical studies. Exp Neurol. 2021; 335: 113518. doi: 10.1016/j.expneurol.2020.113518. PMID: 33144066Rabinstein A.A. Update on treatment of acute ischemic stroke. Continuum (Minneap Minn). 2020; 26 (2): 268–286. DOI: 10.1212/CON.0000000000000840. PMID: 32224752.Rabinstein A.A. Update on treatment of acute ischemic stroke. Continuum (Minneap Minn). 2020; 26 (2): 268–286. DOI: 10.1212/CON.0000000000000840. PMID: 32224752.Campos-Pires R., Koziakova M., Yonis A., Pau A., Macdonald W., Harris K., Edge C.J. et al. Xenon protects against blast-induced traumatic brain injury in an in vitro model. J Neurotrauma. 2018; 35 (8): 1037–1044. DOI: 10.1089/neu.2017.5360. PMID: 29285980.Campos-Pires R., Koziakova M., Yonis A., Pau A., Macdonald W., Harris K., Edge C.J. et al. Xenon protects against blast-induced traumatic brain injury in an in vitro model. J Neurotrauma. 2018; 35 (8): 1037–1044. DOI: 10.1089/neu.2017.5360. PMID: 29285980.Campos-Pires R., Hirnet T., Valeo F., Ong B.E., Radyushkin K., Aldhoun J., Saville J. et al. Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice. Br J Anaesth. 2019; 123 (1): 60–73. DOI: 10.1016/j.bja.2019.02.032. PMID: 31122738Campos-Pires R., Hirnet T., Valeo F., Ong B.E., Radyushkin K., Aldhoun J., Saville J. et al. Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice. Br J Anaesth. 2019; 123 (1): 60–73. DOI: 10.1016/j.bja.2019.02.032. PMID: 31122738Filev A.D., Silachev D.N., Ryzhkov I.A., Lapin K.N., Babkina A.S., Grebenchikov O.A., Pisarev V.M. Effect of xenon treatment on gene expression in brain tissue after traumatic brain injury in rats. Brain Sci. 2021; 11 (7): 889. DOI: 10.3390/brainsci11070889. PMID: 34356124Filev A.D., Silachev D.N., Ryzhkov I.A., Lapin K.N., Babkina A.S., Grebenchikov O.A., Pisarev V.M. Effect of xenon treatment on gene expression in brain tissue after traumatic brain injury in rats. Brain Sci. 2021; 11 (7): 889. DOI: 10.3390/brainsci11070889. PMID: 34356124Moro F., Fossi F., Magliocca A., Pascente R., Sammali E., Baldini F., Tolomeo D. et al. Efficacy of acute administration of inhaled argon on traumatic brain injury in mice. Br J Anaesth. 2021; 126 (1): 256–264. DOI: 10.1016/j.bja.2020.08.027. PMID: 32977957Moro F., Fossi F., Magliocca A., Pascente R., Sammali E., Baldini F., Tolomeo D. et al. Efficacy of acute administration of inhaled argon on traumatic brain injury in mice. Br J Anaesth. 2021; 126 (1): 256–264. DOI: 10.1016/j.bja.2020.08.027. PMID: 32977957Zhang M., Cui Y., Cheng Y., Wang Q., Sun H. The neuroprotective effect and possible therapeutic application of xenon in neurological diseases. J Neurosci Res. 2021; 99 (12): 3274–3283. DOI: 10.1002/jnr.24958. PMID: 34716615Zhang M., Cui Y., Cheng Y., Wang Q., Sun H. The neuroprotective effect and possible therapeutic application of xenon in neurological diseases. J Neurosci Res. 2021; 99 (12): 3274–3283. DOI: 10.1002/jnr.24958. PMID: 34716615Maze M., Laitio T. Neuroprotective properties of xenon. Mol Neurobiol. 2020; 57 (1): 118–124. DOI: 10.1007/s12035-019-01761-z. PMID: 31758401Maze M., Laitio T. Neuroprotective properties of xenon. Mol Neurobiol. 2020; 57 (1): 118–124. DOI: 10.1007/s12035-019-01761-z. PMID: 31758401Wang J., Li R., Peng Z., Hu B., Rao X., Li J. HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE/NF-kB signaling pathways. Int J Mol Med. 2020; 45 (1): 61–80. DOI: 10.3892/ijmm.2019.4402. PMID: 31746367.Wang J., Li R., Peng Z., Hu B., Rao X., Li J. HMGB1 participates in LPS-induced acute lung injury by activating the AIM2 inflammasome in macrophages and inducing polarization of M1 macrophages via TLR2, TLR4, and RAGE/NF-kB signaling pathways. Int J Mol Med. 2020; 45 (1): 61–80. DOI: 10.3892/ijmm.2019.4402. PMID: 31746367.Zewinger S., Reiser J., Jankowski V., Alansary D., Hahm E., Triem S., Klug M. et al. Apolipoprotein C3 induces inflammation and organ damage by alternative inflammasome activation. Nat Immunol. 2020; 21 (1): 30–41. DOI: 10.1038/s41590-019-0548-1. PMID: 31819254Zewinger S., Reiser J., Jankowski V., Alansary D., Hahm E., Triem S., Klug M. et al. Apolipoprotein C3 induces inflammation and organ damage by alternative inflammasome activation. Nat Immunol. 2020; 21 (1): 30–41. DOI: 10.1038/s41590-019-0548-1. PMID: 31819254Mitsui Y., Hou L., Huang X., Odegard K.C., Pereira L.M., Yuki K. Volatile anesthetic sevoflurane attenuates toll-like receptor 1/2 activation. Anesth Analg. 2020; 131 (2): 631–639. DOI: 10.1213/ANE.0000000000004741. PMID: 32149756Mitsui Y., Hou L., Huang X., Odegard K.C., Pereira L.M., Yuki K. Volatile anesthetic sevoflurane attenuates toll-like receptor 1/2 activation. Anesth Analg. 2020; 131 (2): 631–639. DOI: 10.1213/ANE.0000000000004741. PMID: 32149756Brücken A., Kurnaz P., Bleilevens C., Derwall M., Weis J., Nolte K., Rossaint R. et al. Dose dependent neuroprotection of the noble gas argon after cardiac arrest in rats is not mediated by K (ATP)-channel opening. Resuscitation. 2014; 85 (6): 826–32. DOI: 10.1016/j.resuscitation.2014.02.014. PMID: 24582739.Brücken A., Kurnaz P., Bleilevens C., Derwall M., Weis J., Nolte K., Rossaint R. et al. Dose dependent neuroprotection of the noble gas argon after cardiac arrest in rats is not mediated by K (ATP)-channel opening. Resuscitation. 2014; 85 (6): 826–32. DOI: 10.1016/j.resuscitation.2014.02.014. PMID: 24582739.Lemoine S., Blanchart K., Souplis M., Lemaitre A., Legallois D., Coulbault L., Simard C. et al. Argon exposure induces postconditioning in myocardial ischemia-reperfusion. J Cardiovasc Pharmacol Ther. 2017; 22 (6): 564–573. DOI: 10.1177/1074248417702891. PMID: 28381122.Lemoine S., Blanchart K., Souplis M., Lemaitre A., Legallois D., Coulbault L., Simard C. et al. Argon exposure induces postconditioning in myocardial ischemia-reperfusion. J Cardiovasc Pharmacol Ther. 2017; 22 (6): 564–573. DOI: 10.1177/1074248417702891. PMID: 28381122.Mayer B., Soppert J., Kraemer S., Schemmel S., Beckers C., Bleilevens C., Rossaint R. et al. Argon induces protective effects in cardiomyocytes during the second window of preconditioning. Int J Mol Sci. 2016; 17 (7): 1159. DOI: 10.3390/ijms17071159. PMID: 27447611.Mayer B., Soppert J., Kraemer S., Schemmel S., Beckers C., Bleilevens C., Rossaint R. et al. Argon induces protective effects in cardiomyocytes during the second window of preconditioning. Int J Mol Sci. 2016; 17 (7): 1159. DOI: 10.3390/ijms17071159. PMID: 27447611.Ulbrich F., Kaufmann K., Roesslein M., Wellner F., Auwärter V., Kempf J., Loop T. et al. Argon mediates anti-apoptotic signaling and neuroprotection via inhibition of toll-Like receptor 2 and 4. PLoS One. 2015; 10 (12): e0143887. DOI: 10.1371/journal.pone.0143887. PMID: 26624894.Ulbrich F., Kaufmann K., Roesslein M., Wellner F., Auwärter V., Kempf J., Loop T. et al. Argon mediates anti-apoptotic signaling and neuroprotection via inhibition of toll-Like receptor 2 and 4. PLoS One. 2015; 10 (12): e0143887. DOI: 10.1371/journal.pone.0143887. PMID: 26624894.Ulbrich F., Lerach T., Biermann J., Kaufmann K.B., Lagreze W.A., Buerkle H., Loop T. et al. Argon mediates protection by interleukin-8 suppression via a TLR2/TLR4/STAT3/NF-kB pathway in a model of apoptosis in neuroblastoma cells in vitro and following ischemia-reperfusion injury in rat retina in vivo. J Neurochem. 2016; 138 (6): 859–73. DOI: 10.1111/jnc.13662. PMID: 27167824Ulbrich F., Lerach T., Biermann J., Kaufmann K.B., Lagreze W.A., Buerkle H., Loop T. et al. Argon mediates protection by interleukin-8 suppression via a TLR2/TLR4/STAT3/NF-kB pathway in a model of apoptosis in neuroblastoma cells in vitro and following ischemia-reperfusion injury in rat retina in vivo. J Neurochem. 2016; 138 (6): 859–73. DOI: 10.1111/jnc.13662. PMID: 27167824Spaggiari S., Kepp O., Rello-Varona S., Chaba K., Adjemian S., Pype J., Galluzzi L. et al. Antiapoptotic activity of argon and xenon. Cell Cycle. 2013; 12 (16): 2636–42. DOI: 10.4161/cc.25650. PMID: 23907115Spaggiari S., Kepp O., Rello-Varona S., Chaba K., Adjemian S., Pype J., Galluzzi L. et al. Antiapoptotic activity of argon and xenon. Cell Cycle. 2013; 12 (16): 2636–42. DOI: 10.4161/cc.25650. PMID: 23907115Fahlenkamp A.V., Rossaint R., Coburn M. Neuroprotektion durch edelgase: neue entwicklungen und erkenntnisse. [Neuroprotection by noble gases: new developments and insights]. Anaesthesist. 2015; 64 (11): 855-858. (in German). DOI: 10.1007/s00101-015-0079-6. PMID: 26329914Fahlenkamp A.V., Rossaint R., Coburn M. Neuroprotektion durch edelgase: neue entwicklungen und erkenntnisse. [Neuroprotection by noble gases: new developments and insights]. Anaesthesist. 2015; 64 (11): 855-858. (in German). DOI: 10.1007/s00101-015-0079-6. PMID: 26329914Fahlenkamp A.V., Rossaint R., Haase H., Al Kassam H., Ryang Y.M., Beyer C., Coburn M. The noble gas argon modifies extracellular signal-regulated kinase 1/2 signaling in neurons and glial cells. Eur J Pharmacol. 2012; 674 (2-3): 104–111. DOI: 10.1016/j.ejphar.2011.10.045. PMID: 22094065.Fahlenkamp A.V., Rossaint R., Haase H., Al Kassam H., Ryang Y.M., Beyer C., Coburn M. The noble gas argon modifies extracellular signal-regulated kinase 1/2 signaling in neurons and glial cells. Eur J Pharmacol. 2012; 674 (2-3): 104–111. DOI: 10.1016/j.ejphar.2011.10.045. PMID: 22094065.Zhao H., Mitchell S., Ciechanowicz S., Savage S., Wang T., Ji X., Ma D. Argon protects against hypoxic-ischemic brain injury in neonatal rats through activation of nuclear factor (erythroid-derived 2)-like 2. Oncotarget. 2016; 7 (18): 25640–51. DOI: 10.18632/oncotarget.8241. PMID: 27016422Zhao H., Mitchell S., Ciechanowicz S., Savage S., Wang T., Ji X., Ma D. Argon protects against hypoxic-ischemic brain injury in neonatal rats through activation of nuclear factor (erythroid-derived 2)-like 2. Oncotarget. 2016; 7 (18): 25640–51. DOI: 10.18632/oncotarget.8241. PMID: 27016422Zhao H., Mitchell S., Koumpa S., Cui Y.T., Lian Q., Hagberg H., Johnson M.R. et al. Heme oxygenase-1 mediates neuroprotection conferred by argon in combination with hypothermia in neonatal hypoxia-ischemia brain injury. Anesthesiology. 2016; 125 (1): 180–92. DOI: 10.1097/ALN.0000000000001128. PMID: 27065095.Zhao H., Mitchell S., Koumpa S., Cui Y.T., Lian Q., Hagberg H., Johnson M.R. et al. Heme oxygenase-1 mediates neuroprotection conferred by argon in combination with hypothermia in neonatal hypoxia-ischemia brain injury. Anesthesiology. 2016; 125 (1): 180–92. DOI: 10.1097/ALN.0000000000001128. PMID: 27065095.Harris K., Armstrong S.P., Campos-Pires R., Kiru L., Franks N.P., Dickinson R. Neuroprotection against traumatic brain injury by xenon, but not argon, is mediated by inhibition at the N-methylD-aspartate receptor glycine site. Anesthesiology. 2013; 119 (5): 1137–48. DOI: 10.1097/ALN.0b013e3182a2a265. PMID: 23867231Harris K., Armstrong S.P., Campos-Pires R., Kiru L., Franks N.P., Dickinson R. Neuroprotection against traumatic brain injury by xenon, but not argon, is mediated by inhibition at the N-methylD-aspartate receptor glycine site. Anesthesiology. 2013; 119 (5): 1137–48. DOI: 10.1097/ALN.0b013e3182a2a265. PMID: 23867231David H.N., Haelewyn B., Risso J.-J., Abraini J.H. Modulation by the noble gas argon of the catalytic and thrombolytic efficiency of tissue plasminogen activator. Naunyn Schmiedebergs Arch Pharmacol 2013; 386 (1): 91-5. DOI: 10.1007/s00210-012-0809-0. PMID: 23142817David H.N., Haelewyn B., Risso J.-J., Abraini J.H. Modulation by the noble gas argon of the catalytic and thrombolytic efficiency of tissue plasminogen activator. Naunyn Schmiedebergs Arch Pharmacol 2013; 386 (1): 91-5. DOI: 10.1007/s00210-012-0809-0. PMID: 23142817Höllig A., Weinandy A., Liu J., Clusmann H., Rossaint R., Coburn M. Beneficial properties of argon after experimental subarachnoid hemorrhage: early treatment reduces mortality and influences hippocampal protein expression. Crit Care Med. 2016; 44 (7): e520-9. DOI: 10.1097/CCM.0000000000001561. PMID: 26751611Höllig A., Weinandy A., Liu J., Clusmann H., Rossaint R., Coburn M. Beneficial properties of argon after experimental subarachnoid hemorrhage: early treatment reduces mortality and influences hippocampal protein expression. Crit Care Med. 2016; 44 (7): e520-9. DOI: 10.1097/CCM.0000000000001561. PMID: 26751611Zhuang L., Yang T., Zhao H., Fidalgo A.R., Vizcaychipi M.P., Sanders R.D., Yu B. et al. The protective profile of argon, helium, and xenon in a model of neonatal asphyxia in rats. Crit Care Med. 2012; 40 (6): 1724–1730. DOI: 10.1097/CCM.0b013e3182452164. PMID: 22610177Zhuang L., Yang T., Zhao H., Fidalgo A.R., Vizcaychipi M.P., Sanders R.D., Yu B. et al. The protective profile of argon, helium, and xenon in a model of neonatal asphyxia in rats. Crit Care Med. 2012; 40 (6): 1724–1730. DOI: 10.1097/CCM.0b013e3182452164. PMID: 22610177Fahlenkamp A.V., Coburn M., de Prada A., Gereitzig N., Beyer C., Haase H., Rossaint R. et al. Expression analysis following argon treatment in an in vivo model of transient middle cerebral artery occlusion in rats. Med Gas Res. 2014; 4: 11. DOI: 10.1186/2045-9912-4-11. PMID: 25671080Fahlenkamp A.V., Coburn M., de Prada A., Gereitzig N., Beyer C., Haase H., Rossaint R. et al. Expression analysis following argon treatment in an in vivo model of transient middle cerebral artery occlusion in rats. Med Gas Res. 2014; 4: 11. DOI: 10.1186/2045-9912-4-11. PMID: 25671080Ulbrich F., Schallner N., Coburn M., Loop T., Lagrèze W.A., Biermann J., Goebel U. Argon inhalation attenuates retinal apoptosis after ischemia/reperfusion injury in a time- and dose-dependent manner in rats. PLoS One. 2014; 9 (12): e115984. DOI: 10.1371/journal.pone.0115984. PMID: 25535961Ulbrich F., Schallner N., Coburn M., Loop T., Lagrèze W.A., Biermann J., Goebel U. Argon inhalation attenuates retinal apoptosis after ischemia/reperfusion injury in a time- and dose-dependent manner in rats. PLoS One. 2014; 9 (12): e115984. DOI: 10.1371/journal.pone.0115984. PMID: 25535961Ulbrich F., Kaufmann K.B., Coburn M., Lagrèze W.A., Roesslein M., Biermann J., Buerkle H. et al. Neuroprotective effects of argon are mediated via an ERK-1/2 dependent regulation of heme-oxygenase-1 in retinal ganglion cells. J Neurochem. 2015; 134 (4): 717–727. DOI: 10.1111/jnc.13115. Epub 2015. PMID: 25876941Ulbrich F., Kaufmann K.B., Coburn M., Lagrèze W.A., Roesslein M., Biermann J., Buerkle H. et al. Neuroprotective effects of argon are mediated via an ERK-1/2 dependent regulation of heme-oxygenase-1 in retinal ganglion cells. J Neurochem. 2015; 134 (4): 717–727. DOI: 10.1111/jnc.13115. Epub 2015. PMID: 25876941Abraini J.H., Kriem B., Balon N., Rostain J.-C., Risso J.J. Gammaaminobutyric acid neuropharmacological investigations on narcosis produced by nitrogen, argon, or nitrous oxide. Anesth Analg. 2003; 96 (3): 746–749. DOI: 10.1213/01.ANE.0000050282.14291.38. PMID: 12598256 32. Faure A., Bruzzese L., Steinberg J.-G., Jammes Y., Torrents J., Berdah S.V., Garnier E. et al. Effectiveness of pure argon for renal transplant preservation in a preclinical pig model of heterotopic autotransplantation. J Transl Med. 2016; 14: 40. DOI: 10.1186/s12967-016-0795-y. PMID: 26847569Abraini J.H., Kriem B., Balon N., Rostain J.-C., Risso J.J. Gammaaminobutyric acid neuropharmacological investigations on narcosis produced by nitrogen, argon, or nitrous oxide. Anesth Analg. 2003; 96 (3): 746–749. DOI: 10.1213/01.ANE.0000050282.14291.38. PMID: 12598256 32. Faure A., Bruzzese L., Steinberg J.-G., Jammes Y., Torrents J., Berdah S.V., Garnier E. et al. Effectiveness of pure argon for renal transplant preservation in a preclinical pig model of heterotopic autotransplantation. J Transl Med. 2016; 14: 40. DOI: 10.1186/s12967-016-0795-y. PMID: 26847569Liu J., Nolte K., Brook G., Liebenstund L., Weinandy A., Höllig A., Veldeman M. et al. Post-stroke treatment with argon attenuated brain injury, reduced brain inflammation and enhanced M2 microglia/macrophage polarization: a randomized controlled animal study. Crit Care. 2019; 23 (1): 198. DOI: 10.1186/s13054-019-2493-7. PMID: 31159847Liu J., Nolte K., Brook G., Liebenstund L., Weinandy A., Höllig A., Veldeman M. et al. Post-stroke treatment with argon attenuated brain injury, reduced brain inflammation and enhanced M2 microglia/macrophage polarization: a randomized controlled animal study. Crit Care. 2019; 23 (1): 198. DOI: 10.1186/s13054-019-2493-7. PMID: 31159847De Roux Q., Lidouren F., Kudela A., Slassi L., Kohlhauer M., Boissady E., Chalopin M. et al. Argon attenuates multiorgan failure in relation with HMGB1 inhibition. Int J Mol Sci. 2021; 22 (6): 3257. DOI: 10.3390/ijms22063257. PMID: 33806919De Roux Q., Lidouren F., Kudela A., Slassi L., Kohlhauer M., Boissady E., Chalopin M. et al. Argon attenuates multiorgan failure in relation with HMGB1 inhibition. Int J Mol Sci. 2021; 22 (6): 3257. DOI: 10.3390/ijms22063257. PMID: 33806919Qi H., Soto-Gonzalez L., Krychtiuk K.A., Ruhittel S., Kaun C., Speidl W.S., Kiss A. et al. Pretreatment with argon protects human cardiac myocyte-like progenitor cells from oxygen glucose deprivation-induced cell death by activation of AKT and differential regulation of mapkinases. Shock. 2018; 49 (5): 556–563. DOI: 10.1097/SHK.0000000000000998. PMID: 29658909Qi H., Soto-Gonzalez L., Krychtiuk K.A., Ruhittel S., Kaun C., Speidl W.S., Kiss A. et al. Pretreatment with argon protects human cardiac myocyte-like progenitor cells from oxygen glucose deprivation-induced cell death by activation of AKT and differential regulation of mapkinases. Shock. 2018; 49 (5): 556–563. DOI: 10.1097/SHK.0000000000000998. PMID: 29658909Grüßer L., Blaumeiser-Debarry R., Krings M., Kremer B., Höllig A., Rossaint R., Coburn M. Argon attenuates the emergence of secondary injury after traumatic brain injury within a 2-hour incubation period compared to desflurane: an in vitro study. Med Gas Res. 2017; 7 (2): 93–100. DOI: 10.4103/2045-9912.208512. PMID: 28744361Grüßer L., Blaumeiser-Debarry R., Krings M., Kremer B., Höllig A., Rossaint R., Coburn M. Argon attenuates the emergence of secondary injury after traumatic brain injury within a 2-hour incubation period compared to desflurane: an in vitro study. Med Gas Res. 2017; 7 (2): 93–100. DOI: 10.4103/2045-9912.208512. PMID: 28744361Creed J., Cantillana-Riquelme V., Yan B.H., Ma S., Chu D., Wang H., Turner D.A. et al. Argon inhalation for 24 h after closed-head injury does not improve recovery, neuroinflammation, or neurologic outcome in mice. Neurocrit Care. 2021; 34 (3): 833–843. DOI: 10.1007/s12028-020-01104-0. PMID: 32959200Creed J., Cantillana-Riquelme V., Yan B.H., Ma S., Chu D., Wang H., Turner D.A. et al. Argon inhalation for 24 h after closed-head injury does not improve recovery, neuroinflammation, or neurologic outcome in mice. Neurocrit Care. 2021; 34 (3): 833–843. DOI: 10.1007/s12028-020-01104-0. PMID: 32959200David H.N., Dhilly M., Degoulet M., Poisnel G., Meckler C., Vallée N., Blatteau J.É. et al. Argon blocks the expression of locomotor sensitization to amphetamine through antagonism at the vesicular monoamine transporter-2 and mu-opioid receptor in the nucleus accumbens. Transl Psychiatry. 2015; 5 (7): e594. DOI: 10.1038/tp.2015.27. PMID: 26151922David H.N., Dhilly M., Degoulet M., Poisnel G., Meckler C., Vallée N., Blatteau J.É. et al. Argon blocks the expression of locomotor sensitization to amphetamine through antagonism at the vesicular monoamine transporter-2 and mu-opioid receptor in the nucleus accumbens. Transl Psychiatry. 2015; 5 (7): e594. DOI: 10.1038/tp.2015.27. PMID: 26151922Zhuang L., Yang T., Zhao H., Fidalgo A.R., Vizcaychipi M.P., Sanders R.D., Yu B. et al. The protective profile of argon, helium, and xenon in a model of neonatal asphyxia in rats. Crit Care Med. 2012; 40 (6): 1724–1730. DOI: 10.1097/CCM.0b013e3182452164. PMID: 22610177Zhuang L., Yang T., Zhao H., Fidalgo A.R., Vizcaychipi M.P., Sanders R.D., Yu B. et al. The protective profile of argon, helium, and xenon in a model of neonatal asphyxia in rats. Crit Care Med. 2012; 40 (6): 1724–1730. DOI: 10.1097/CCM.0b013e3182452164. PMID: 22610177Koziakova M., Harris K., Edge C.J., Franks N.P., White I.L., Dickinson R. Noble gas neuroprotection: xenon and argon protect against hypoxic-ischaemic injury in rat hippocampus in vitro via distinct mechanisms. Br J Anaesth. 2019; 123 (5): 601–609. DOI: 10.1016/j.bja.2019.07.010. PMID: 31470983Koziakova M., Harris K., Edge C.J., Franks N.P., White I.L., Dickinson R. Noble gas neuroprotection: xenon and argon protect against hypoxic-ischaemic injury in rat hippocampus in vitro via distinct mechanisms. Br J Anaesth. 2019; 123 (5): 601–609. DOI: 10.1016/j.bja.2019.07.010. PMID: 31470983Shakova F.M.; Kirova Y.I.; Silachev D.N.; Romanova G.A.; Morozov S.G. Protective effects of PGC-1α activators on ischemic stroke in a rat model of photochemically induced thrombosis. Brain Sci. 2021; 11 (3): 325. DOI: 10.3390/brainsci11030325. PMID: 33806692Shakova F.M.; Kirova Y.I.; Silachev D.N.; Romanova G.A.; Morozov S.G. Protective effects of PGC-1α activators on ischemic stroke in a rat model of photochemically induced thrombosis. Brain Sci. 2021; 11 (3): 325. DOI: 10.3390/brainsci11030325. PMID: 33806692De Ryck M., Van Reempts J., Borgers M., Wauquier A., Janssen P.A. Photochemical stroke model: flunarizine prevents sensorimotor deficits after neocortical infarcts in rats. Stroke. 1989; 20 (10): 1383–1390. DOI: 10.1161/01.str.20.10.1383. PMID: 2799870De Ryck M., Van Reempts J., Borgers M., Wauquier A., Janssen P.A. Photochemical stroke model: flunarizine prevents sensorimotor deficits after neocortical infarcts in rats. Stroke. 1989; 20 (10): 1383–1390. DOI: 10.1161/01.str.20.10.1383. PMID: 2799870Jolkkonen J., Puurunen K., Rantakömi S., Härkönen A., Haapalinna A., Sivenius J. Behavioral effects of the alpha (2)-adrenoceptor an tagonist, atipamezole, after focal cerebral ischemia in rats. Eur J Pharmacol. 2000; 400 (2–3): 211–219. DOI: 10.1016/s0014-2999(00)00409-x. PMID: 10988336Jolkkonen J., Puurunen K., Rantakömi S., Härkönen A., Haapalinna A., Sivenius J. Behavioral effects of the alpha (2)-adrenoceptor an tagonist, atipamezole, after focal cerebral ischemia in rats. Eur J Pharmacol. 2000; 400 (2–3): 211–219. DOI: 10.1016/s0014-2999(00)00409-x. PMID: 10988336Silachev D.N., Uchevatkin A.A., Pirogov Yu.A., Zorov D.B., Isaev N.K. Comparative evaluation of two methods for studies of experimental focal ischemia: magnetic resonance tomography and triphenyltetrazoleum detection of brain injuries. Bull Exp Biol Med. 2009; 147 (2): 269–272. DOI: 10.1007/s10517-009-0489-z. PMID: 19513437Silachev D.N., Uchevatkin A.A., Pirogov Yu.A., Zorov D.B., Isaev N.K. Comparative evaluation of two methods for studies of experimental focal ischemia: magnetic resonance tomography and triphenyltetrazoleum detection of brain injuries. Bull Exp Biol Med. 2009; 147 (2): 269–272. DOI: 10.1007/s10517-009-0489-z. PMID: 19513437Isaev N.K., Novikova S.V., Stelmashook E.V., Barskov I.V., Silachev D.N., Khaspekov L.G., Skulachev V.P. et al. Mitochondria-targeted plastoquinone antioxidant SkQR1 decreases trauma-induced neurological deficit in rat. Biochemistry (Mosc). 2012; 77 (9): 996–999. DOI: 10.1134/S0006297912090052. PMID: 23157258Isaev N.K., Novikova S.V., Stelmashook E.V., Barskov I.V., Silachev D.N., Khaspekov L.G., Skulachev V.P. et al. Mitochondria-targeted plastoquinone antioxidant SkQR1 decreases trauma-induced neurological deficit in rat. Biochemistry (Mosc). 2012; 77 (9): 996–999. DOI: 10.1134/S0006297912090052. PMID: 23157258Голубев А. М. Модели ишемического инсульта (обзор). Общая реаниматология. 2020; 16 (1): 59–72. DOI: 10.15360/1813-9779-2020-1-59-72Golubev A.M. Models of ischemic stroke (Review). General Reanimatology/Obshchaya Reanimatologya. 2020; 16 (1): 59–72. (in Russ.). DOI: 10.15360/1813-9779-2020-1-59-72Ma S., Chu D., Li L., Creed J.A., Ryang Y.-M., Sheng H., Yang W. et al. Argon inhalation for 24 hours after onset of permanent focal cerebral ischemia in rats provides neuroprotection and improves neurologic outcome. Crit Care Med. 2019; 47 (8): e693–e699. DOI: 10.1097/CCM.0000000000003809. PMID: 31094741Ma S., Chu D., Li L., Creed J.A., Ryang Y.-M., Sheng H., Yang W. et al. Argon inhalation for 24 hours after onset of permanent focal cerebral ischemia in rats provides neuroprotection and improves neurologic outcome. Crit Care Med. 2019; 47 (8): e693–e699. DOI: 10.1097/CCM.0000000000003809. PMID: 31094741Zhang L., Chopp M., Zhang Y., Xiong Y., Li C., Sadry N., Rhaleb I. et al. Diabetes mellitus impairs cognitive function in middle-aged rats and neurological recovery in middle-aged rats after stroke. Stroke. 2016; 47 (8): 2112–2118. DOI: 10.1161/STROKEAHA.115.012578. PMID: 27387991Zhang L., Chopp M., Zhang Y., Xiong Y., Li C., Sadry N., Rhaleb I. et al. Diabetes mellitus impairs cognitive function in middle-aged rats and neurological recovery in middle-aged rats after stroke. Stroke. 2016; 47 (8): 2112–2118. DOI: 10.1161/STROKEAHA.115.012578. PMID: 27387991Shin S.S., Hwang M., Diaz-Arrastia R., Kilbaugh T.J. Inhalational gases for neuroprotection in traumatic brain injury. J Neurotrauma. 2021; 38 (19): 2634–2651. DOI: 10.1089/neu.2021.0053. PMID: 33940933Shin S.S., Hwang M., Diaz-Arrastia R., Kilbaugh T.J. Inhalational gases for neuroprotection in traumatic brain injury. J Neurotrauma. 2021; 38 (19): 2634–2651. DOI: 10.1089/neu.2021.0053. PMID: 33940933Заржецкий Ю.В., Борисов К.Ю., Гребенчиков О.А., Шайбакова В.Л., Левиков Д.И., Лихванцев В.В. Влияние севофлурана на функциональное восстановление животных, перенесших системную остановку кровообращения. Общая реаниматология. 2012; 8 (2): 15. DOI: 10.15360/1813-9779-2012-2-15Zarzhetsky Yu.V., Borisov K.Yu., Grebenchikov O.A., Shaibakova V.L., Levikov D.I., Likhvantsev V.V. Effect of sevoflurane on functional recovery in animals sustaining systemic circulatory arrest. General Reanimatology/ Obshchaya Reanimatologya. 2012; 8 (2): 15. (In Russ.). DOI: 10.15360/1813-9779-2012-2-15Гребенчиков О.А., Аврущенко М.Ш., Борисов К.Ю., Ильин Ю.В., Лихванцев В.В. Нейропротекторные эффекты севофлурана на модели тотальной ишемии-реперфузии. Клиническая Патофизиология. 2014; 2; 57–65. eLIBRARY ID: 26292775Grebenshchikov O.A., Avrushchenko M.Sh., Borisov K.Yu., Ilyin Yu.V., Likhvantsev V.V. Neuroprotective effects of sevoflurane on the model of total ischemia-reperfusion. Clinical Pathophysiology/ Klinicheskaya Patofysiologiya. 2014; 2; 57–65. (in Russ.). eLIBRARY ID: 26292775Likhvantsev V.V., Landoni G., Levikov D.I., Grebenchikov O.A., Skripkin Y.V., Cherpakov R. A. Sevoflurane versus total intravenous anesthesia for isolated coronary artery bypass surgery with cardiopulmonary bypass: a randomized trial. J Cardiothorac Vasc Anesth. 2016; 30 (5): 1221–1227. DOI: 10.1053/j.jvca.2016.02.030. PMID: 27431595Likhvantsev V.V., Landoni G., Levikov D.I., Grebenchikov O.A., Skripkin Y.V., Cherpakov R. A. Sevoflurane versus total intravenous anesthesia for isolated coronary artery bypass surgery with cardiopulmonary bypass: a randomized trial. J Cardiothorac Vasc Anesth. 2016; 30 (5): 1221–1227. DOI: 10.1053/j.jvca.2016.02.030. PMID: 27431595Silachev D.N., Usatikova E.A., Pevzner I.B., Zorova L.D., Babenko V.A., Gulyaev M.V., Pirogov Y.A. et al. Effect of anesthetics on efficiency of remote ischemic preconditioning. Biochemistry (Mosc). 2017; 82 (9): 1006–1016. DOI: 10.1134/S0006297917090036. PMID: 28988529.Silachev D.N., Usatikova E.A., Pevzner I.B., Zorova L.D., Babenko V.A., Gulyaev M.V., Pirogov Y.A. et al. Effect of anesthetics on efficiency of remote ischemic preconditioning. Biochemistry (Mosc). 2017; 82 (9): 1006–1016. DOI: 10.1134/S0006297917090036. PMID: 28988529.Боева Е.А., Гребенчиков О.А. Органопротективные свойств аргона (обзор). Общая реаниматология. 2022; 18 (5): 44–59. DOI: 10.15360/1813-9779-2022-5-44-59.Boeva E.A., Grebenchikov O.A. Organoprotective Properties of Argon (Review). General Reanimatology/Obshchaya Reanimatologya. 2022; 18 (5): 44–59. (in Russ.). DOI: 10.15360/1813-9779-2022-5-44-59.David H.N., Haelewyn B., Degoulet M., Colomb D.G. Jr, Risso J.J., Abraini J.H. Ex vivo and in vivo neuroprotection induced by argon when given after an excitotoxic or ischemic insult. PLoS One. 2012; 7 (2): e30934. DOI: 10.1371/journal.pone.0030934. PMID: 22383981David H.N., Haelewyn B., Degoulet M., Colomb D.G. Jr, Risso J.J., Abraini J.H. Ex vivo and in vivo neuroprotection induced by argon when given after an excitotoxic or ischemic insult. PLoS One. 2012; 7 (2): e30934. DOI: 10.1371/journal.pone.0030934. PMID: 22383981

The authors declare that there are no conflicts of interest present.