Table 2.
In vivo studies employing argon for protection in models of acute cerebral and myocardial injury, for narcosis and for liver regeneration
| Article | Disease | Model | Comparison and duration of treatment | Functional assessment1 | Histopathology | Biochemistry |
|---|---|---|---|---|---|---|
| Models of acute cerebral injury | ||||||
| Höllig et al., 2016[34] | SAH | Endovascular perforation technique | Ar/O2 50/50 | ≈ | Hippocampus DG: ↑ | HIF1α: + |
| Duration: 1 h | Hippocampus CA1: ≈ | HO-1: + | ||||
| Hippocampus CA3/4: ≈ | ||||||
| Zhuang et al., 2012[35] | Perinatal HIE | Right common carotid artery ligation + hypoxia | Ar/O2 70/30 Duration: 90 min | ≈↑ | Hippocampus CA1: ↑ | Bcl-2: + |
| Infarct size: ↑ | ||||||
| Alderliesten et al., 2014[36] | Perinatal HIE | Hypoxia | Ar/room air30-80/70-20 | NA | NA | NA |
| Ar/room air 50/50 | ||||||
| Ar/room air 50/50 + MTH | ||||||
| Duration: 1 h × 3 | ||||||
| Broad et al., 2016[37] | Perinatal HIE | Common bilateral carotid artery occlusion | Ar/O2/N2 45-50/30-21/25-29 + MTH | aEEG: ↑ | Neocortex: ↑ | PCr/pi: + |
| Subcortical: ↑ | NTP/epp: + | |||||
| Duration: 2-26 h | Lac/NAA: - | |||||
| Zhao et al., 2016[29] | Perinatal HIE | Right common carotid ligation + hypoxia | Ar/O2 70/30 | NA | Neocortex: ↑ | MDA: - |
| Duration: 2 h | Infarct size: ↑ | GSH: + | ||||
| GSSG: - | ||||||
| TNFα, IL-6: - | ||||||
| SOD1, NQO1: + | ||||||
| Zhao et al., 2016[28] | Perinatal HIE | Right common carotid ligation + hypoxia | Ar/O2 70/30 + MTH Ar/O2 70/30 | NA | Infarct size: ↑ | HO-1: + |
| Bcl-2: + | ||||||
| Duration: 2 h | Caspase 3: - | |||||
| NF-kB: - | ||||||
| Hippocampal GFAP: - | ||||||
| Ryang et al., 2011[38] | Ischemic stroke | Transient middle cerebral artery occlusion | Ar/O2 50/50 | ↑ | Neocortex: ↑ | NA |
| Duration: 1 h | Basal ganglia: ↑ | |||||
| Infarct size: ↓ | ||||||
| David et al., 2012[27] | 1. Ischemic stroke | 1. Middle cerebral artery occlusion | 1. Ar/O2 50/50 | 1. ↑ | 1. ≈ | NA |
| 2. Ar/N2/O2 15-75 | 2. ↓ | 2. ↑ | ||||
| 2. Excitotoxicity | 2.Intrastriatal injection of NMDA | Duration: 3 h | ||||
| Fahlenkamp et al., 2014[39] | Ischemic stroke | Transient middle cerebral artery occlusion | Ar/O2 50/50 | NA | Ischemic area: ≈↑ | IL-1β, IL-6: + |
| Duration: 1h | iNOS, TGF-β, NGF: + | |||||
| Ulbrich et al., 2014[40] | Retinal I/R | Anterior chamber hypertension | Ar/O2/N2 25-75/21/4-54 | NA | Ganglional cell: ↑ | Caspase 3: - |
| Bax: - | ||||||
| Duration: 1 h | Bcl-2: - | |||||
| NF-kB: - | ||||||
| Blood WC count: - | ||||||
| Ulbrich et al., 2015[41] | Retinal I/R | Anterior chamber hypertension | Ar/O2/N2 75/21/4 Duration: 1 h | NA | Ganglion cells: ↑ | HSP: - |
| ERK 1-2: + | ||||||
| HO-1: + | ||||||
| Ulbrich et al., 2016[22] | Retinal I/R | Anterior chamber hypertension | Ar/O2/N2 75/21/4 Duration: 1 h | NA | ↑ | IL-8: - |
| MithocondrialΔΨ: + | ||||||
| ROS: - | ||||||
| NF-kB, STAT3: - | ||||||
| Models of acute myocardial injury | ||||||
| Pagel et al., 2007[45] | Infarction | LAD occlusion | Ar/O2 70/30 Duration: 5 mins × 3* | NA | Infarct size: ↑ | NA |
| Ristagno et al., 2014[13] | Cardiac arrest | LAD occlusion + VF | Ar/O2 70/30 Duration: 4 h | cUS: Systolic function (EF) ≈↑ | Infarct size: ≈↑ | hs-cTnT: ≈↑ |
| Lemoine et al., 2017[17] | Infarction | LAD ligation | Ar/O2 80/20 Duration: 20 min | cMR: systolic function (LV volumes, EF) ↑ | NA | NA |
| WMS ↑ | ||||||
| Models of narcosis | ||||||
| Balon et al., 2002[42] | Ar narcosis | Hyperbaric chamber | Ar 2 MPa + O2 0,04 MPa | NA | NA | Striatal DA release: - |
| Duration: 2h | ||||||
| Balon et al., 2003[43] | Ar narcosis | Hyperbaric chamber | Ar 2 MPa + O2 0,04 MPa | First phase of compression → hyperactivity, then hypoactivity | NA | Striatal DA release: - |
| Duration: 100 min | ||||||
| Abraini et al., 2003[44] | Ar narcosis | Hyperbaric chamber | Ar + O2 0,03 MPa Compression rate: 0,1 MPa/min | Increased threshold pressure for loss of righting reflex | NA | NA |
| Models of liver regeneration | ||||||
| Ulmer et al., 2017[53] | Liver regeneration | Partial Hepatectomy | Ar/O2 50/50 | Weight of residual liver: ≈ | Proliferation↓Apoptosis≈ | AST, ALT, bilirubin:≈ |
| BrdU↓ | ||||||
| Ki-67↓ | ||||||
| UNEL≈ | ||||||
| HGF↓ | ||||||
| IL-6↓ | ||||||
| Duration: 1 h# | Liver-body weight ratio: ≈ | TNF≈ | ||||
| ERK 1/2 ≈ | ||||||
*In this study, Ar was administered as pretreatment before MI, #In this study, Ar was administered before injury (preconditioning). ↑: Treatment with Ar was significantly protective compared to control; ≈↑: Treatment with Ar showed a trend toward protection compared to control; ≈: Treatment with Ar was equivalent to control; +: Increased with Ar treatment compared to control; -: Decreased with Ar treatment compared to control; ↓: Treatment with Ar was significantly detrimental. 1functional assessment included: neurological tests for model of acute cerebral injury; myocardial function after acute ischemic injury; and motor assessment under hyperbaric condition. Ar: Argon, O2: Oxygen, N2: Nitrogen, He: Helium, Xe: Xenon, NO: Nitrosous oxide, Ne: Neon, NA: Not available, SAH: Subarachnoid hemorrhage, DG: Dentate gyrus, HIF: hypoxia inducible factor, HO-1: heme oxygenase-1, HIE: hypoxic ischemic encephalopathy, Bcl-2: B-cell lymphoma 2, MTH: Mild therapeutic hypothermia; aEEG: amplitude-integrated electo-encephalogram, PCr/pi: Ratio of phosphocreatine to inorganic phosphate, NTP: Nucleoside triphosphate, epp: Exchangeable phosphate pool, Lac: Lactate, NAA: N-acetylaspartate, MDA: Malondialdehyde, GSH: Glutathione, GSSG: Glutathione disulfide, TNFα: Tumor necrosis factorα, IL: interleukin, SOD: Superoxide dismutase, NQO1: nicotinamide adenine dinucleotide phosphate (NADP) dehydrogenase quinone 1, NF-kB: Nuclear factor-kB, GFAP: Glial fibrillary acid protein, NMDA: N-Methyl-D-aspartic acid, iNOS: inducible nitric oxide synthase, TGF-β: Transforming growth factorβ, NGF: Nerve growth factor, I/R: Ischemia/reperfusion, Bax: Bcl-2-associated X protein, WC: White cells, HSP: Heat shock protein, ERK 1/2: Extracellular signal-regulated kinase, ΔΨ: Membrane potential, ROS: Reactive oxygen species, STAT3: Signal transducer and activator of transcription 3, LAD: Left anterior descending coronary artery, VF: Ventricular fibrillation, cUS: Cardiac ultrasound, EF: Ejection fraction, hs-cTnT: High-sensitivity cardiac troponin T, cMR: Cardiac magnetic resonance, LV: Left ventricle, WMS: Wall motion score, MPa: Megapascal, DA: Dopamine, AST: Aspartate aminotransferase, ALT: Alanine aminotransferase, BrdU: Bromodeoxyuridine, HGF: Hepatocyte growth factor