Neuroprotective effects of argon in an in vivo model of transient middle cerebral artery occlusion in rats*

Ryang, Yu‐Mi; Fahlenkamp, Astrid; Rossaint, Rolf; Wesp, Dominik; Loetscher, Philip D; Beyer, Cordian; Coburn, Mark

doi:10.1097/ccm.0b013e31821209be

Cited by 106 publications

(128 citation statements)

References 28 publications

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“…It was reported that argon was protective against hypoxia-induced injury in cultured neurons 21,22 . In an in vivo model of acute focal cerebral ischaemia in adult rats, exposure to 50% argon significantly reduced infarct volumes and neurological deficits after the occlusion 23 . Although noble gases are chemically inert, they are capable of forming induced dipole, which is attracted to the charge that induced it, or instantaneous dipole, which produces and binds to an induced dipole in a second molecule 24 .…”

Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1 Mediates Neuroprotection Conferred by Argon in Combination with Hypothermia in Neonatal Hypoxia–Ischemia Brain Injury

et al. 2016

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Background Hypoxic–ischemic encephalopathy is a major cause of mortality and disability in the newborn. The authors investigated the protective effects of argon combined with hypothermia on neonatal rat hypoxic–ischemic brain injury. Methods In in vitro studies, rat cortical neuronal cell cultures were challenged by oxygen and glucose deprivation for 90 min and exposed to 70% Ar or N2 with 5% CO2 balanced with O2, at 33°C for 2 h. Neuronal phospho-Akt, heme oxygenase-1 and phospho-glycogen synthase kinase-3β expression, and cell death were assessed. In in vivo studies, neonatal rats were subjected to unilateral common carotid artery ligation followed by hypoxia (8% O2 balanced with N2 and CO2) for 90 min. They were exposed to 70% Ar or N2 balanced with oxygen at 33°, 35°, and 37°C for 2 h. Brain injury was assessed at 24 h or 4 weeks after treatment. Results In in vitro studies, argon–hypothermia treatment increased phospho-Akt and heme oxygenase-1 expression and significantly reduced the phospho-glycogen synthase kinase-3β Tyr-216 expression, cytochrome C release, and cell death in oxygen–glucose deprivation–exposed cortical neurons. In in vivo studies, argon–hypothermia treatment decreased hypoxia/ischemia-induced brain infarct size (n = 10) and both caspase-3 and nuclear factor-κB activation in the cortex and hippocampus. It also reduced hippocampal astrocyte activation and proliferation. Inhibition of phosphoinositide-3-kinase (PI3K)/Akt pathway through LY294002 attenuated cerebral protection conferred by argon–hypothermia treatment (n = 8). Conclusion Argon combined with hypothermia provides neuroprotection against cerebral hypoxia–ischemia damage in neonatal rats, which could serve as a new therapeutic strategy against hypoxic–ischemic encephalopathy.

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Section: Discussionmentioning

confidence: 99%

Heme Oxygenase-1 Mediates Neuroprotection Conferred by Argon in Combination with Hypothermia in Neonatal Hypoxia–Ischemia Brain Injury

et al. 2016

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“…Similar to xenon, argon and helium have shown neuroprotective qualities in vitro (11)(12)(13)(14) and in vivo (13,19) while other members of noble gas family, neon and krypton, lack effect (11). Interestingly helium has also been reported to exhibit both detrimental as well as protective effects (11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

The protective profile of argon, helium, and xenon in a model of neonatal asphyxia in rats*

Zhuang

Yang

Zhao

et al. 2012

Critical Care Medicine

125

130

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Abstract:OBJECTIVE: Xenon provides neuroprotection in multiple animal models however little is known about the other noble gases. The aim of the current study was to compare xenon, argon and helium neuroprotection in a neonatal asphyxia model in MEASUREMENTS AND MAIN RESULTS: Control animals undergoing moderatehypoxic-ischemia endured reduced neuronal survival at 7 days with impaired neurological function at the juvenile age compared with naïve animals. Severe hypoxic-ischemic damage produced a large cerebral infarction in controls. Following moderate hypoxic-ischemia, all three noble gases improved cell survival, brain structural integrity and neurological function on post-natal day 40 compared to nitrogen. Interestingly argon improved cell survival to naïve levels while xenon and helium did not. When tested against more severe hypoxic-ischemic injury only, argon and xenon reduced infarct volume. Furthermore post-injury body weight in moderate insult was lower in the helium treated group compared to the naïve, control and other noble gas treatment groups while in severe injurious setting it is lower in both control and helium treated group than other groups. In the non-directly injured hemisphere argon, helium and xenon increased the expression of Bcl-2 while helium 4 and xenon increased Bcl-xL. In addition, Bax expression was enhanced in the control and helium groups.CONCLUSIONS: These studies indicate that argon and xenon provide neuroprotection against both moderate and severe hypoxia-ischemic brain injury likely via prosurvival proteins synthesis.

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“…Here, the neuroprotective properties of argon are well documented [5,7,9,25]. For example, Ryang et al [16] demonstrated significantly reduced infarct volumes after transient middle cerebral artery occlusion - without, however, influencing acute survival 24 h after the intervention. These positive, encouraging results inspired an investigation into the influence of argon on other organs.…”

Section: Discussionmentioning

confidence: 99%

“…All surgical procedures were performed under inhalation anesthesia as previously described [16]. To evaluate an effect of the inhalant argon, animals were exposed to either 50 vol% argon (argon group) or 50 vol% nitrogen (control group) balanced with 50 vol% oxygen for 60 min prior to injury (preconditioning).…”

Section: Methodsmentioning

confidence: 99%

Argon Delays Initiation of Liver Regeneration after Partial Hepatectomy in Rats

et al. 2017

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Background: The liver can heal up to restitutio ad integrum following damage resulting from various causes. Different studies have demonstrated the protective effect of argon on various cells and organs. To the best of our knowledge, the organ-protective effects of the noble gas argon on the liver have not yet been investigated, although argon appears to influence signal paths that are well-known mediators of liver regeneration. We hypothesized that argon inhalation prior to partial hepatectomy (70%) has a positive effect on the initiation of liver regeneration in rats. Methods: Partial hepatectomy (70%) with or without inhaled argon (50 vol%) was performed for 1 h. Liver tissue was harvested after 3, 36, and 96 h to analyze the mRNA and protein expression of hepatocyte growth factor (HGF), interleukin-6 (IL-6), tumor necrosis factor-α, and extracellular signal-regulated kinase 1/2. Histological tissue samples were prepared for immunohistochemistry (bromodeoxyuridine [BrdU], Ki-67, and TUNEL) and blood was analyzed regarding the effects of argon on liver function. Statistical analyses were performed using 1-way ANOVA followed by the post hoc Tukey-Kramer test. Results: After 3 h, the primary outcome parameter of hepatocyte proliferation was significantly reduced with argon 50 vol% inhalation in comparison to nitrogen inhalation (BrdU: 15.7 ± 9.7 vs. 7.7 ± 3.1 positive cells/1,000 hepatocytes, p = 0.013; Ki-67: 17.6 ± 13.3 vs. 4.7 ± 5.4 positive cells/1,000 hepatocytes, p = 0.006). This was most likely mediated by significant downregulation of HGF (after 3 h: 5.2 ± 3.2 vs. 2.3 ± 1.0 fold, p = 0.032; after 96 h: 2.1 ± 0.5 vs. 1.3 ± 0.3 fold, p = 0.029) and IL-6 (after 3 h: 43.7 ± 39.6 vs. 8.5 ± 9.2 fold, p = 0.032). Nevertheless, we could detect no significant effect on the weight of the residual liver, liver-body weight ratio, or liver blood test results after argon inhalation. Conclusion: Impairment of liver regeneration was apparent after argon 50 vol% inhalation that was most probably mediated by downregulation of HGF and IL-6 in the initial phase. However, the present study was not adequately powered to prove that argon has detrimental effects on the liver. Further studies are needed to evaluate the effects of argon on livers with preexisting conditions as well as on ischemia-reperfusion models.

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Neuroprotective effects of argon in an in vivo model of transient middle cerebral artery occlusion in rats*

Cited by 106 publications

References 28 publications

Heme Oxygenase-1 Mediates Neuroprotection Conferred by Argon in Combination with Hypothermia in Neonatal Hypoxia–Ischemia Brain Injury

Heme Oxygenase-1 Mediates Neuroprotection Conferred by Argon in Combination with Hypothermia in Neonatal Hypoxia–Ischemia Brain Injury

The protective profile of argon, helium, and xenon in a model of neonatal asphyxia in rats*

Argon Delays Initiation of Liver Regeneration after Partial Hepatectomy in Rats

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