Treatment with inhaled Argon: a systematic review of pre-clinical and clinical studies with meta-analysis on neuroprotective effect.

BACKGROUND: Argon (Ar) has been proposed as a potential therapeutic agent in multiple clinical conditions, specifically in organ protection. However, conflicting data on pre-clinical models, together with a great variability in Ar administration protocols and outcome assessments, have been reported. The aim of this study was to review evidence on treatment with Ar, with an extensive investigation on its neuroprotective effect, and to summarise all tested administration protocols. METHODS: Using the PubMed database, all existing pre-clinical and clinical studies on the treatment with Ar were systematically reviewed (registration: https://doi.org/10.17605/OSF.IO/7983D). Study titles and abstracts were screened, extracting data from relevant studies post full-text review. Exclusion criteria included absence of full text and non-English language. Furthermore, meta-analysis was also performed to assess Ar potential as neuroprotectant agent in different clinical conditions: cardiac arrest, traumatic brain injury, ischemic stroke, perinatal hypoxic-ischemic encephalopathy, subarachnoid haemorrhage. Standardised mean differences for neurological, cognitive and locomotor, histological, and physiological measures were evaluated, through appropriate tests, clinical, and laboratory variables. In vivo studies were evaluated for risk of bias using the Systematic Review Center for Laboratory Animal Experimentation tool, while in vitro studies underwent assessment with a tool developed by the Office of Health Assessment and Translation. FINDINGS: The systematic review detected 60 experimental studies (16 in vitro, 7 ex vivo, 31 in vivo, 6 with both in vitro and in vivo) investigating the role of Ar. Only one clinical study was found. Data from six in vitro and nineteen in vivo studies were included in the meta-analyses. In pre-clinical models, Ar administration resulted in improved neurological, cognitive and locomotor, and histological outcomes without any change in physiological parameters (i.e., absence of adverse events). INTERPRETATION: This systematic review and meta-analysis based on experimental studies supports the neuroprotective effect of Ar, thus providing a rationale for potential translation of Ar treatment in humans. Despite adherence to established guidelines and methodologies, limitations in data availability prevented further analyses to investigate potential sources of heterogeneity due to study design. FUNDING: This study was funded in part by Italian Ministry of Health-Current researchIRCCS and by Ministero della Salute Italiano, Ricerca Finalizzata, project no. RF 2019-12371416.

Noble Gas Anions: An Overview of Strategies and Bonding Motifs.

This review article aims to provide an overview of the strategies employed to prepare noble gas anions under different environments and experimental conditions, and of the bonding motifs typically occurring in these species. Observed systems include anions fixed into synthesized salts, detected in the gas phase or in high-pressure devices. The major role of the theoretical calculations is also highlighted, not only in support of the experiments, but also as effective in predicting still unreported species. The chemistry of noble gas anions overall appears as a varied and rich paint, offering fascinating opportunities for both experimentalists and theoreticians.

Observation of magnetic amplification using dark spins.

Quantum amplification enables the enhancement of weak signals and is of great importance for precision measurements, such as biomedical science and tests of fundamental symmetries. Here, we observe a previously unexplored magnetic amplification using dark noble-gas nuclear spins in the absence of pump light. Such dark spins exhibit remarkable coherence lasting up to 6 min and the resilience against the perturbations caused by overlapping alkali-metal gas. We demonstrate that the observed phenomenon, referred to as "dark spin amplification," significantly magnifies magnetic field signals by at least three orders of magnitude. As an immediate application, we showcase an ultrasensitive magnetometer capable of measuring subfemtotesla fields in a single 500-s measurement. Our approach is generic and can be applied to a wide range of noble-gas isotopes, and we discuss promising optimizations that could further improve the current signal amplification up to [Formula: see text] with [Formula: see text]Ne, [Formula: see text] with [Formula: see text]Xe, and [Formula: see text] with [Formula: see text]He. This work unlocks opportunities in precision measurements, including searches for ultralight dark matter with sensitivity well beyond the supernova-observation constraints.

Neuroprotective Effects of Krypton Inhalation on Photothrombotic Ischemic Stroke.

This is the first in vivo study to investigate the neuroprotective effects of krypton on focal cerebral ischemia. The aim of the study was to analyze the effect of 2 h of inhalation of a krypton-oxygen mixture (Kr 70%/O2 30%) on the recovery of neurological functions and the degree of brain damage in rats after photoinduced ischemic stroke (PIS) and to investigate the possible mechanisms responsible for this neuroprotection. Experiments were performed on male Wistar rats weighing 250-300 g (n = 32). Animals were randomized into four groups. Two groups (n = 20) underwent photoinduced ischemic stroke, followed by 2 h of inhalation of krypton-oxygen mixture consisting of Kr 70%/O2 30% or a nitrogen-oxygen breathing mixture consisting of N2 70%/O2 30%, followed by neurological examinations on days 3 and 7. The other two groups (n = 12) received only gas mixtures of the same concentration and exposure duration as in those in the PIS groups, then Western blot analysis of the potential molecular mechanisms was performed. The results of the study show that treatment with the krypton-oxygen mixture consisting of Kr 70%/O2 30% improves the neurological status on day 7 of observation, reduces the lesion volume according to the MRI examination and the number of Iba-1- and caspase-3-positive cells in the damaged area, promotes the activation of neoangiogenesis (an increase in the von Willebrand factor), and reduces the penumbra area and the number of NeuN-positive cells in it on day 14 of observation. Inhalation of the krypton-oxygen mixture also significantly increases the levels of phosphorylated AKT kinase (protein kinase B) and glycogen synthase kinase 3b (pGSK3b) and promotes the expression of transcription factor Nrf2, which was accompanied by the lowered expression of transcription factor NFkB (p50). Thus, we showed pronounced neuroprotection induced by krypton inhalation after stroke and identified the signaling pathways that may be responsible for restoring neurological functions and reducing damage.

Efficient injection of gas tracers into rivers: A tool to study Surface water-Groundwater interactions.

Surface water (SW) - groundwater (GW) interactions exhibit complex spatial and temporal patterns often studied using tracers. However, most natural and artificial tracers have limitations in studying SW-GW interactions, particularly if no significant contrasts in concentrations between SW and GW exist or can be maintained for long durations. In such context, (noble) gases have emerged as promising alternatives to add to the available tracer methods, especially with the recent development of portable mass spectrometers, which enable continuous monitoring of dissolved gas concentrations directly in the field. However, long-duration gas injection into river water presents logistical challenges. To overcome this limitation, we present an efficient and robust diffusion-injection apparatus for labeling large amounts of river water. Our setup allows fine, real-time control of the gas injection rate, and is suitable for extended injection durations and different gas species. To illustrate the effectiveness of our approach, we present a case study where helium (He) is used as an artificial tracer to study river water infiltration into an alluvial aquifer. Our injection of He as a tracer increased the dissolved He concentration of the river water by one order of magnitude compared to air-saturated water concentration for 35 days. This experiment yields valuable information on travel times from the river to a pumping well and on the mixing ratios between freshly infiltrated river water and regional groundwater.

Design of simulated-gas calibration source and self-attenuation correction methods for radioactive noble gas measurement with HPGe detector.

In this study, to achieve accurate measurement of radioactive noble gas and enhance the precision of efficiency calibration, a relatively low-cost and low-density simulated-gas calibration source (SGCS) was produced from polyurethane foam with a density of ρ = 0.098 g cm-3. Using SGCS with a Marinelli beaker geometry, the efficiency calibration was applied to a BE5030, 50.5% relative efficiency HPGe detector in an energy range of 59.54 keV∼1836.06 keV. Then, taking the 81 keV gamma-ray emitted by 133Xe as an example, due to the density difference between the SGCS and the 133Xe gas sample, it is necessary to correct for self-attenuation effects. Therefore, a semi-empirical function for self-attenuation correction was established by using LabSOCS software and XCOM. Upon validation, the relative deviation of efficiency calibration values between the SGCS and the LabSOCS of 133Xe under the density of 0.001 g cm-3 to 0.01 g cm-3 was about 3%. After using the self-attenuation correction method established in this study, the results verified a good consistency of the efficiency calculated by SGCS and LabSOCS software.

Noble gas dative bonding with coinage metal carbene complexes: A theoretical study.

The structure and stability of noble gas (Ng) bound [NHCM]+ complexes (M = Cu, Ag, and Au) were investigated using Quantum chemical calculations. Dissociation energies, enthalpy, and free energy changes were computed to comprehend the stability of these Ng-bonded complexes. The nature of interactions associated to the bonding between metal and noble gas atoms was studied through the computation of electron density-based descriptors. Detailed electronic structure study revealed electron donation from the noble gas atoms towards the metal center, resulting in the formation of dative bonds.

Argon inhalation attenuates systemic inflammation and rescues lung architecture during experimental neonatal sepsis.

PURPOSE: Neonatal sepsis is a systemic inflammatory infection common in premature infants and a leading cause of mortality. Argon is an emerging interest in the field of noble gas therapy. Neonates with severe sepsis are frequently mechanically ventilated creating an opportunity for inhalation therapy. We aimed to investigate argon inhalation as a novel experimental therapy in neonatal sepsis. METHODS: Sepsis was established in C57BL/6 neonatal mice by a lipopolysaccharide intraperitoneal injection on postnatal day 9. Septic pup mice were exposed to room air as well as non-septic controls. In the argon group, septic pup mice were exposed to argon (70% Ar, 30% O2) for 6 h in a temperature-controlled environment. RESULTS: At 6 h, survival was significantly enhanced when septic mice received argon compared to septic controls. Serum profiles of cytokine release were significantly attenuated as well as lung architecture restored. CONCLUSIONS: Our findings suggest that argon inhalation as a novel treatment for neonatal sepsis, reducing mortality and counteracting the acute systemic inflammatory response in the blood and preserving the architecture of the lung. This research can contribute to a paradigm shift in the treatment and outcome of neonates with sepsis.

Estimation of ecosystem respiration and photosynthesis in supersaturated stream water downstream of a hydropower plant.

The estimation of whole stream metabolism, as determined by photosynthesis and respiration, is critical to our understanding of carbon cycling and carbon subsidies to aquatic food-webs. The mass development of aquatic plants is a worldwide problem for human activities and often occurs in regulated rivers, altering biodiversity and ecosystem functions. Hydropower plants supersaturate water with gases and prevent the use of common whole stream metabolism models to estimate ecosystem respiration. Here we used the inert noble gas argon to parse out biological from physical processes in stream metabolism calculations. We coupled the O2:Ar ratio determined by gas chromatography in grab samples with in-situ oxygen concentrations measured by an optode to estimate aquatic plant photosynthesis and ecosystem respiration during supersaturation events through a parsimonious approach. The results compared well with a more complicated two-station model based on O2 mass balances in non-supersatured water, and with associated changes in dissolved CO2 (or dissolved inorganic carbon). This new method provides an independent approach to evaluate alternative corrections of dissolved oxygen data (e.g. through the use of total dissolved gases) in long term studies. The use of photosynthesis-irradiance models allows the determination of light parameters such as the onset of light saturation or low light use efficiency, which could be used for inverse modelling. The use of the O2:Ar approach to correct for oversaturation may become more applicable with the emergence of portable mass inlet mass spectrometers (MIMS). Photosynthesis was modest (2.9-5.8 g O2 m2 day-1) compared to other rivers with submerged vegetation, likely indicating nutrient co-limitations (CO2, inorganic N and P). Respiration was very low (-2.1 to -3.9 g O2 m2 day-1) likely due to a lack of allochthonous carbon supply and sandy sediment.

Bader's Topological Bond Path Does Not Necessarily Indicate Stabilizing Interaction-Proof Studies Based on the Ng@[3n]cyclophane Endohedral Complexes.

According to Bader's quantum theory of atoms in molecules (QTAIM), the simultaneous presence of a bond path and the corresponding bond critical point between any two atoms is both a necessary and sufficient condition for the atoms to be bonded to one another. In principle, this means that this pair of atoms should make a stabilizing contribution to the molecular system. However, the multitude of so-called counterintuitive bond paths strongly suggests that this statement is not necessarily true. Particularly 'troublesome' are endohedral complexes, in which encapsulation-enforced proximity between the trapped guest (e.g., an atom) and the host's cage system usually 'produces' many counterintuitive bond paths. In the author's opinion, the best evidence to demonstrate the repulsive nature of the intra-cage guest⋯host interaction is the use of some trapping systems containing small escape channels and then showing that the initially trapped entity spontaneously escapes outside the host's cage during geometry optimization of the initially built guest@host endohedral complex. For this purpose, a group of 24 Ng@[3n]cyclophane (3≤n≤6) endohedral complexes is used. As a result, arguments are presented showing that Bader's topological bond path does not necessarily indicate a stabilizing interaction.

Complexes of HXeY with HX (Y, X = F, Cl, Br, I): Symmetry-Adapted Perturbation Theory Study and Anharmonic Vibrational Analysis.

A comprehensive analysis of the intermolecular interaction energy and anharmonic vibrations of 41 structures of the HXeY⋯HX (X, Y = F, Cl, Br, I) family of noble-gas-compound complexes for all possible combinations of Y and X was conducted. New structures were identified, and their interaction energies were studied by means of symmetry-adapted perturbation theory, up to second-order corrections: this provided insight into the physical nature of the interaction in the complexes. The energy components were discussed, in connection to anharmonic frequency analysis. The results show that the induction and dispersion corrections were the main driving forces of the interaction, and that their relative contributions correlated with the complexation effects seen in the vibrational stretching modes of Xe-H and H-X. Reasonably clear patterns of interaction were found for different structures. Our findings corroborate previous findings with better methods, and provide new data. These results suggest that the entire group of the studied complexes can be labelled as "naturally blueshifting", except for the complexes with HI.

On the Nature of the Partial Covalent Bond between Noble Gas Elements and Noble Metal Atoms.

This article provides a discussion on the nature of bonding between noble gases (Ng) and noble metals (M) from a quantum chemical perspective by investigating compounds such as NgMY (Y=CN, O, NO3, SO4, CO3), [NgM-(bipy)]+, NgMCCH, and MCCNgH complexes, where M=Cu, Ag, Au and Ng=Kr-Rn, with some complexes containing the lighter noble gas atoms as well. Despite having very low chemical reactivity, noble gases have been observed to form weak bonds with noble metals such as copper, gold, and silver. In this study, we explore the factors that contribute to this unusual bonding behavior, including the electronic structure of the atoms involved and the geometric configuration of the concerned fragments. We also investigate the metastable nature of the resulting complexes by studying the energetics of their possible dissociation and internal isomerization channels. The noble gas-binding ability of the bare metal cyanides are higher than most of their bromide counterparts, with CuCN and AgCN showing higher affinity than their chloride analogues as well. In contrast, the oxides seem to have lower binding power than their corresponding halides. In the oxide and the bipyridyl complexes, the Ng-binding ability follows the order Au > Cu > Ag. The dissociation energies calculated, considering the zero-point energy correction for possible dissociation channels, increase as we move down the noble gas group. The bond between the noble gases and the noble metals in the complexes are found to have comparable weightage of orbital and electrostatic interactions, suggestive of a partial covalent nature. The same is validated from the topological analysis of electron density.

Coordination of noble gases by alkali-metal-like superatom cation Be3 B.

Quantum chemical calculations were carried out to investigate the noble gas binding ability of Be3 B+ cluster. Calculations reveal that heavier noble gas atoms (ArXe) form stable complexes with this cluster. Detailed bonding analyses reveal that the noble gas atoms act as donor fragment in the formation of Ng → Be donor-acceptor bonds. Three noble gas atoms can consecutively form bonds with the Be atom of the Be3 B+ cluster.

Argon pharmacokinetics: a solubility measurement technique.

The noble gas argon has demonstrated biological activity that may prove useful as a medical intervention. Pharmacokinetics, the disposition of the drug molecule in the body through time, is fundamental necessary knowledge to drug discovery, development and even post-marketing. The fundamental measurement in pharmacokinetic studies is blood concentration of the molecule (and its metabolites) of interest. While a physiologically based model of argon pharmacokinetics has appeared in the literature, no experimental data have been published. Thus, argon pharmaceutical development requires measurement of argon solubility in blood. This paper reports on the development of a technique based on mass spectrometry for measuring argon solubility in liquids, including blood, to be further employed in pharmacokinetics testing of argon. Based on a prototype, results are reported from sensitivity experiments using ambient air, water and rabbit blood. The key takeaway is that the system was sensitive to argon during all of the testing. We believe the technique and prototype of the quadrupole mass spectrometer gas analyzer will be capable of inferring argon pharmacokinetics through the analysis of blood samples.

Evaluating the sources and fate of nitrate in riparian aquifers under agricultural land using in situ-measured noble gases, stable isotopes, and metabolic genes.

Riparian zones with their buffering ability and abundant water supply are often subjected to intensive agricultural activities. We investigated a riparian aquifer located near a stream in South Korea that recently experienced sharply decreasing groundwater levels and elevated nitrate (NO3-) concentrations, which were attributed to local agricultural activities. Our goal was to identify the predominant nitrogen sources and NO3- removal processes. Multiple approaches including geochemical and isotopic tracers, land-use analysis, metabolic gene quantification, and inert gas tracers were used to elucidate groundwater and nutrient dynamics in stream-side granitic aquifers. The dual isotopic composition of NO3- identified manure and sewage as the major sources of NO3- contamination. Denitrification was the dominant NO3- removal process in the aquifer, as demonstrated by the negative relationship between δ15N and δ18O values in NO3-and NO3-/Cl-. Denitrification and anammox genes were also observed in microbial communities of the aquifer throughout the study site, suggesting that these processes support effective natural NO3- attenuation in groundwater. A mixing model constructed using a catchment-scale dataset including SiO2 concentrations and δ18O-H2O suggested that mixing with paddy soil water was the major driver of denitrification in the aquifer at the study site, where impervious layers provided anaerobic conditions for natural NO3- attenuation. Denitrification reduced the NO3- flux into the nearby stream by up to 114.4 NO3- kg/ha/y (26 kg N/ha/y). The N2 generated by denitrification did not accumulate in the groundwater, but mostly escaped from groundwater to the atmosphere, as demonstrated by the degassed signature of dissolved inert gases below the air saturated water level. This study identified the predominant NO3- sources and conceptualized N cycling in the heavily developed agricultural riparian aquifer using multiple tracers, demonstrating that NO3- is partially removed through denitrification and possibly anammox while N2 mostly escapes into the atmosphere.

Beryllium bonding with noble gas atoms.

Quantum chemical calculations were carried out to investigate the nature of the bonding between a neutral Be3 ring and noble gas atom. Electronic structure calculation for these complexes was carried out at different computational levels in association with natural bond orbital, quantum theory of atoms in molecules, electron localization function, symmetry adapted perturbation theory, and molecular electrostatic potential surface analysis of Be3 complexes. The Be atoms in the Be3 moiety are chemically bonded to one another, with the BeBe bond dissociation energy being ~125 kJ mol-1 . The Be3 ring interacts with the noble gases through non-covalent interactions. The binding energies of the noble gas atoms with the Be3 ring increases with increase in their atomic number. The non-covalent interaction index, density overlap region indicator and independent gradient model analyses reveal the presence of non-covalent inter-fragment interactions in the complexes. Energy decomposition analysis reveals that dispersion plays the major role towards stabilizing these systems.

Overview of temporary radioxenon background measurement campaigns conducted for the CTBTO between 2008 and 2018.

The Comprehensive Nuclear-Test-Ban Treaty (CTBT) specifies that an overall network of at least 40 International Monitoring System (IMS) stations should monitor the presence of radioxenon in the atmosphere upon its entry into force. The measurement of radioxenon concentrations in the air is one of the major techniques to detect underground nuclear explosions. It is, together with radionuclide particulate monitoring, the only component of the network able to confirm whether an event originates from a nuclear test, leaving the final proof to on-site inspection. Correct and accurate interpretation of radioxenon detections by State Signatories is a key parameter of the verification regime of the Preparatory Commission for the Comprehensive Nuclear-Test-Ban Treaty Organization (CTBTO). In this context, the discrimination between the highly variable radioxenon background generated by normal operations of nuclear facilities and CTBT-relevant events is a challenging, but critical, task. To this end, the radioxenon background that can be expected at IMS noble gas systems must be sufficiently characterized and understood. All activities conducted to study the global radioxenon background are focused on the calibration and performance of the verification system as described in the Treaty. The unique CTBTO noble gas system network is designed to optimally covering the globe. By the end of 2019, 31 systems were put in operation, 25 of which being already certified. It took two decades from the first experimental setup of noble gas system in the field to reach this stage of maturity. In the meantime, it was an urgent need to gain empirical evidence of atmospheric radioxenon concentrations with the full spectrum of characteristics that IMS noble gas systems may be observing. This experience was significantly advanced through temporary measurement campaigns. Their objective was to gain the additional necessary knowledge for a correct understanding and categorization of radioxenon detections. The site selection for these campaigns put emphasis on regions with low coverage by the initially few experimental noble gas systems at IMS locations or where potential interferences with normal background might be observed. Short-term measurements were first initiated in 2008. Sites of potential interest were identified, and campaigns up to few weeks were performed. Based on the findings of these short campaigns, transportable systems were procured by the CTBTO. Longer temporary measurement campaigns were started afterwards and operated by local hosts in different regions of the globe. Site selections were based on purely scientific criteria. Objectives of the measurement campaigns were continually reassessed, and projects were designed to meet the scientific needs for radioxenon background understanding as required for nuclear explosion monitoring. As of today, several thousands of samples have been collected and measured. Spectra of temporary measurement campaigns were (and are still) analysed in the International Data Centre (IDC). As they are not part of the CTBT monitoring system, no IDC product is generated. Analysis results are stored in a non-operational database of the CTBTO and made available, together with raw data, to authorized users of States Signatories through a Secure Web Portal (SWP) and to scientific institutions for approved research projects through a virtual Data Exploitation Centre (vDEC) after signing a cost-free confidentiality agreement (https://www.ctbto.org/specials/vdec). This paper aims at providing an overview of the temporary measurement campaigns conducted by the CTBTO since the very first field measurements. It lays out scientific results in a systematic approach. This overview demonstrates the asset of radioxenon background measurement data that have been collected with a wide variety of characteristics that may be observed at IMS stations. It bears a tremendous opportunity for development, enhancement and validation of methodologies for CTBT monitoring. In 2018, a campaign started in Japan with transportable noble gas systems in the vicinity of the IMS station RN38 in Takasaki. It will be described separately once the measurements are completed.

BH4 Ng+ (Ar-Rn): Viable Compounds with a B-Ng Covalent Bond.

In this work, we explore, using high-level calculations, the ability of BH4 + to interact with noble gases. The He system is energetically unstable, while the Ne system could only be observed at cryogenic temperatures. In the case of the Ar, Kr and Xe systems, all are energetically stable, even at room temperature. The different chemical bond descriptors reveal a covalent character between B and the noble gas from Ar to Rn. However, this interaction gradually weakens the multicentric bond between the boron atom and the H2 fragment. Thus, although BH4 Rn+ exhibits a strong covalent bond, it tends to dissociate at room temperature into BH2 Rn+ +H2 .

Can the Fluxionality in Borospherene Influence the Confinement-Induced Bonding between Two Noble Gas Atoms?

A density functional theory study is performed to determine the stability and bonding in the neon dimer inside the B30N30 fullerene cage, the fluxional B40 cage, and within non-fluxional cages such as B12N12 and C60. The nature of bonding in the Ne2 encapsulated B40 is compared with the that in other cages in an attempt to determine whether any possible alterations are brought about by the dynamical nature of the host cage apart from the associated confinement effects. The bonding analysis includes the natural bond order (NBO), Bader's Atoms-in-Molecules electron density analysis (AIM), and energy decomposition analysis (EDA), revealing the non-covalent nature of the interactions between the Ne atoms and that between the Ne and the cage atoms. The formation of all the Ne2@cage systems is thermochemically unfavourable, the least being that for the B30N30 cage, which can easily be made favourable at lower temperatures. The Ne-Ne distance is lowest in the smallest cage and increases as the cage size increase due to steric relaxation experienced by the dimer. The dynamical picture of the systems is investigated by performing ab initio molecular dynamics simulations using the atom-centred density matrix propagation (ADMP) technique, which shows the nature of the movement of the dimer inside the cages, and by the fact that since it moves as a single entity, a weak bonding force holds them together, apart from their proven kinetic stability.

Noble gas and neuroprotection: From bench to bedside.

In recent years, inert gases such as helium, argon, and xenon have gained considerable attention for their medical value. Noble gases present an intriguing scientific paradox: although extremely chemically inert, they display a remarkable spectrum of clinically useful biological properties. Despite a relative paucity of knowledge about their mechanisms of action, some noble gases have been used successfully in clinical practice. The neuroprotection elicited by these noble gases has been investigated in experimental animal models of various types of brain injuries, such as traumatic brain injury, stroke, subarachnoid hemorrhage, cerebral ischemic/reperfusion injury, and neurodegenerative diseases. Collectively, these central nervous system injuries are a leading cause of morbidity and mortality every year worldwide. Treatment options are presently limited to thrombolytic drugs and clot removal for ischemic stroke, or therapeutic cooling for other brain injuries before the application of noble gas. Currently, there is increasing interest in noble gases as novel treatments for various brain injuries. In recent years, neuroprotection elicited by particular noble gases, xenon, for example, has been reported under different conditions. In this article, we have reviewed the latest in vitro and in vivo experimental and clinical studies of the actions of xenon, argon, and helium, and discuss their potential use as neuroprotective agents.