Noble gas neuroprotection: xenon and argon protect against hypoxic–ischaemic injury in rat hippocampus in vitro via distinct mechanisms

Abstract

Background: Noble 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. Methods: We used an in vitro model of hypoxiaeischaemia 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. Results: Both 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. Conclusions: Xenon and argon are equally effective as neuroprotectants against hypoxiaeischaemia in vitro, with both gases preventing injury development. Although xenon's neuroprotective effect may be mediated by inhibition of the Nmethyl-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.

Argon inhibits reactive oxygen species oxidative stress via the miR-21-mediated PDCD4/PTEN pathway to prevent myocardial ischemia/reperfusion injury

“…Recently, inert gas has become a research hotspot because of its potential organ protective effect. Argon, as one of the main components, has a protective effect on nerves and myocardium after ischemia reperfusion injury [3][4][5][6]. In vivo, 30% and 50% argon pre-treatment significantly reduced the apoptosis and inflammation level and improved the cell survival rate in human cardiomyocytes by AKT activation and differential regulation of MAP kinases [4].…”

Update of the organoprotective properties of xenon and argon: from bench to beside

“…The best effect in vivo was shown for a concentration of 50 Vol% inhaled argon [101]. Recently, Koziakova et al compared the neuroprotective effects of xenon and argon in the same model of organotypic hippocampal brain slices [109]. Both substances impaired the neurologic injury to the same extent.…”

The Function of the NMDA Receptor in Hypoxic-Ischemic Encephalopathy

“…The noble gas xenon is shown to have neuroprotective effects in hypoxic-ischemic models through inhibiting NMDA receptors by competing for the binding of glycine in many in vitro and in vivo animal models (Hobbs et al, 2008;Zhuang et al, 2010;Faulkner et al, 2011;Zhao et al, 2013;Juul and Ferriero, 2014;Alam et al, 2017;Rüegger et al, 2018;Koziakova et al, 2019).…”

“…The noble gas xenon is shown to have neuroprotective effects in hypoxic-ischemic models through inhibiting NMDA receptors by competing for the binding of glycine in many in vitro and in vivo animal models ( Hobbs et al, 2008 ; Zhuang et al, 2010 ; Faulkner et al, 2011 ; Zhao et al, 2013 ; Juul and Ferriero, 2014 ; Alam et al, 2017 ; Rüegger et al, 2018 ; Koziakova et al, 2019 ). Xenon can also be used as an adjuvant with hypothermia therapy to treat neonatal HIE and has been proven to be effective in reducing brain injury and improving long-term recovery ( Ma et al, 2005 ; Chakkarapani et al, 2010 ; Amer and Oorschot, 2018 ).…”