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.

Argon neuroprotection in ischemic stroke and its underlying mechanism.

Ischemic stroke (IS), primarily caused by cerebrovascular obstruction, results in severe neurological deficits and has emerged as a leading cause of death and disability worldwide. Recently, there has been increasing exploration of the neuroprotective properties of the inert gas argon. Argon has exhibited impressive neuroprotection in many in vivo and ex vivo experiments without signs of adverse effects, coupled with the advantages of being inexpensive and easily available. However, the efficient administration strategy and underlying mechanisms of neuroprotection by argon in IS are still unclear. This review summarizes current research on the neuroprotective effects of argon in IS with the goal to provide effective guidance for argon application and to elucidate the potential mechanisms of argon neuroprotection. Early and appropriate argon administration at as high a concentration as possible offers favorable neuroprotection in IS. Argon inhalation has been shown to provide some long-term protection benefits. Argon provides the anti-oxidative stress, anti-inflammatory and anti-apoptotic cytoprotective effects mainly around Toll-like receptor 2/4 (TLR2/4), mediated by extracellular signal-regulated kinase 1/2 (ERK1/2), nuclear factor (erythroid-derived 2)-like 2 (Nrf2), nuclear factor kappa-B (NF-ĸB) and B-cell leukemia/lymphoma 2 (Bcl-2). Therefore, argon holds significant promise as a novel clinical neuroprotective gas agent for ischemic stroke after further researches to identify the optimal application strategy and elucidate the underlying mechanism.

Comparative assessment of direct and indirect cold atmospheric plasma effects, based on helium and argon, on human glioblastoma: an in vitro and in vivo study.

Recent research has highlighted the promising potential of cold atmospheric plasma (CAP) in cancer therapy. However, variations in study outcomes are attributed to differences in CAP devices and plasma parameters, which lead to diverse compositions of plasma products, including electrons, charged particles, reactive species, UV light, and heat. This study aimed to evaluate and compare the optimal exposure time, duration, and direction-dependent cellular effects of two CAPs, based on argon and helium gases, on glioblastoma U-87 MG cancer cells and an animal model of GBM. Two plasma jets were used as low-temperature plasma sources in which helium or argon gas was ionized by high voltage (4.5 kV) and frequency (20 kHz). In vitro assessments on human GBM and normal astrocyte cell lines, using MTT assays, flow cytometry analysis, wound healing assays, and immunocytochemistry for Caspase3 and P53 proteins, demonstrated that all studied plasma jets, especially indirect argon CAP, selectively induced apoptosis, hindered tumor cell growth, and inhibited migration. These effects occurred concurrently with increased intracellular levels of reactive oxygen species and decreased total antioxidant capacity in the cells. In vivo results further supported these findings, indicating that single indirect argon and direct helium CAP therapy, equal to high dose Temozolomide treatment, induced tumor cell death in a rat model of GBM. This was concurrent with a reduction in tumor size observed through PET-CT scan imaging and a significant increase in the survival rate. Additionally, there was a decrease in GFAP protein levels, a significant GBM tumor marker, and an increase in P53 protein expression based on immunohistochemical analyses. Furthermore, Ledge beam test analysis revealed general motor function improvement after indirect argon CAP therapy, similar to Temozolomide treatment. Taken together, these results suggest that CAP therapy, using indirect argon and direct helium jets, holds great promise for clinical applications in GBM treatment.

Positive Neuroprotective Effect of Argon Inhalation after Photochemically Induced Ischemic Stroke Model in Rats.

We studied the effect of 2-h inhalation of argon-oxygen mixture (Ar 70%/O2 30%) after photochemically induced stroke and on days 2 and 3 after stroke modeling on the severity of neurological deficit and brain damage (by MRI data) in Wistar rats. Neurological deficit was assessed within 14 days using the limb placement test. MRI and histological study of the brain with an assessment of the size of damage were performed on day 14 after ischemia. Significant differences were obtained in limb placement scores on days 3, 7, and 14, as well as in the volume of ischemic focus by MRI in comparison with the control (ischemia+N2 70%/O2 30%). Inhalation of argon-oxygen mixture for 2 h a day over 3 days after photoinduced stroke decreased the volume of brain damage by 2 times and reduced the severity of neurological deficit.

Effects of Argon Gas Plasma Treatment on Biocompatibility of Nanostructured Titanium.

In this study, we applied argon plasma treatment to titanium surfaces with nanostructures deposited by concentrated alkali treatment and investigated the effects on the surface of the material and the tissue surrounding an implant site. The results showed that the treatment with argon plasma removed carbon contaminants and increased the surface energy of the material while the nanoscale network structure deposited on the titanium surface remained in place. Reactive oxygen species reduced the oxidative stress of bone marrow cells on the treated titanium surface, creating a favorable environment for cell proliferation. Good results were observed in vitro evaluations using rat bone marrow cells. The group treated with argon plasma exhibited the highest apatite formation in experiments using simulated body fluids. The results of in vivo evaluation using rat femurs revealed that the treatment improved the amount of new bone formation around an implant. Thus, the results demonstrate that argon plasma treatment enhances the ability of nanostructured titanium surfaces to induce hard tissue differentiation and supports new bone formation around an implant site.

Watermelon stomach: clinical aspects and treatment with argon plasma coagulation / Ectasia vascular do antro gástrico ("watermelon stomach"): aspectos clínicos e tratamento com coagulação com plasma de argônio

BACKGROUND: Gastric antral vascular ectasia is a disorder whose pathogenetic mechanism is unknown. The endoscopic treatment with argon plasma coagulation has been considered one of the best endoscopic therapeutic options. AIM: To analyze the endoscopic and clinical features of gastric antral vascular ectasia and its response to the argon plasma coagulation treatment. PATIENTS AND METHODS: Eighteen patients were studied and classified into two groups: group 1 - whose endoscopic aspect was striped (watermelon) or of the diffuse confluent type; group 2 - diffuse spotty nonconfluent endoscopic aspect. RESULTS: Group 1 with eight patients, all having autoimmune antibodies, but one, whose antibodies were not searched for. Three were cirrhotic and three had hypothyroidism. All had gastric mucosa atrophy. In group 2, with 10 patients, all had non-immune liver disease, with platelet levels below 90.000. Ten patients were submitted to argon plasma coagulation treatment, with 2 to 36 months of follow-up. Lesions recurred in all patients who remained in the follow-up program and one did not respond to treatment for acute bleeding control. CONCLUSION: There seem to be two distinct groups of patients with gastric antral vascular ectasia: one related to immunologic disorders and other to non-immune chronic liver disease and low platelets. The endoscopic treatment using argon plasma coagulation had a high recurrence in the long-term evaluation.

RACIONAL: "Watermelon stomach" ou ectasia vascular do antro gástrico é uma doença de etiopatogenia desconhecida. O tratamento endoscópico através da coagulação com plasma de argônio é considerado uma das melhores opções terapêuticas. OBJETIVO: Analisar os aspectos clínicos e endoscópicos da ectasia vascular do antro gástrico e a resposta ao tratamento com coagulação com plasma de argônio. PACIENTES E MÉTODOS: Dezoito pacientes foram estudados e classificados em dois grupos: grupo I - oito pacientes que exibiam ectasia vascular do antro gástrico de aspecto difuso confluente ou estriado. Grupo II - 10 pacientes que apresentavam aspecto difuso pontilhado não-confluente. RESULTADOS: Todos os pacientes do grupo I apresentavam auto-anticorpos, exceto um paciente no qual não foi pesquisado. Três eram cirróticos, três tinham hipotireoidismo e todos apresentavam gastrite atrófica. No grupo II, todos tinham doença hepática não-autoimune, com plaquetas menores que 90.000. Dez pacientes foram submetidos a tratamento com coagulação com plasma de argônio, com 2 a 36 meses de seguimento. A ectasia vascular do antro gástrico recorreu em todos os pacientes que continuaram em acompanhamento e um paciente não respondeu ao tratamento para controle de sangramento agudo. CONCLUSÃO: Observou-se a existência de dois grupos distintos de pacientes com ectasia vascular do antro gástrico: um grupo associado a distúrbios imunológicos e outro com doença hepática não auto-imune e plaquetopenia. O tratamento com coagulação com plasma de argônio apresentou alta recurrência das ectasias vasculares.