Dose dependent neuroprotection of the noble gas argon after cardiac arrest in rats is not mediated by KATP—Channel opening

Brücken, Anne; Kurnaz, Pınar; Berne, Christian; Derwall, Matthias; Weis, Joachim; Nolte, Kay; Rossaint, Rolf; Fries, Michael

doi:10.1016/j.resuscitation.2014.02.014

Cited by 46 publications

(60 citation statements)

References 31 publications

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“…The morphological extent of brain damage (at least for some regions) was reduced compared to controls. In rats dose dependency of the beneficial effect after resuscitation was demonstrated with better neurological outcome after treatment with 70% argon than with 40% [29]. …”

Section: Discussionmentioning

confidence: 99%

“…Further, using electrophysiology (patch clamp technique) no effect of argon on NMDA-mediated currents was found, likewise for currents flowing through TREK-1, a two-pore-domain potassium channel [40]. In an in vivo study (resuscitation rat model), pretreatment with a K ATP -channel blocker (5-Hydroxydecanoate = 5HD) also failed to impact argon’s beneficial effect [29]. Therefore, neither NMDA receptors nor potassium channels seem to be involved.…”

Section: Discussionmentioning

confidence: 99%

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Argon: Systematic Review on Neuro- and Organoprotective Properties of an “Inert” Gas

Höllig

Schug

Fahlenkamp

et al. 2014

IJMS

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Argon belongs to the group of noble gases, which are regarded as chemically inert. Astonishingly some of these gases exert biological properties and during the last decades more and more reports demonstrated neuroprotective and organoprotective effects. Recent studies predominately use in vivo or in vitro models for ischemic pathologies to investigate the effect of argon treatment. Promising data has been published concerning pathologies like cerebral ischemia, traumatic brain injury and hypoxic ischemic encephalopathy. However, models applied and administration of the therapeutic gas vary. Here we provide a systematic review to summarize the available data on argon’s neuro- and organoprotective effects and discuss its possible mechanism of action. We aim to provide a summary to allow further studies with a more homogeneous setting to investigate possible clinical applications of argon.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Argon: Systematic Review on Neuro- and Organoprotective Properties of an “Inert” Gas

Höllig

Schug

Fahlenkamp

et al. 2014

IJMS

Self Cite

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“…Routinely used vasopressors (e.g., vasopressin, epinephrine, or their combination), albeit have beneficial effects in the initial phase of CPR, exacerbate myocardial ischemia/reperfusion injury and fail to significantly improve survival and neurological outcome to hospital discharge (Lin et al, 2014;Yu et al, 2013). Novel pharmacological approaches able to ease CPR and also to minimize the general adverse consequences of CA are, therefore, needed (Brücken et al, 2014;Kida et al, 2012;Kurita et al, 2010;Lee et al, 2012;Norman et al, 2011;Parnia et al, 2014;Yu et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

“…Besides further studies on therapeutic hypothermiamainly known as efficient treatment for neuroprotection during CA -novel approaches to protect the heart and brain are under investigation, including hydrogen sulfide donors, activators of cholinergic pathways, carvedilol, and argon (Brücken et al, 2014;Kida et al, 2012;Kurita et al, 2010;Lee et al, 2012;Norman et al, 2011;Parnia et al, 2014;Yu et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Protective effects of the melanocortin analog NDP-α-MSH in rats undergoing cardiac arrest

Ottani

Neri

Canalini

et al. 2014

European Journal of Pharmacology

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We previously reported that melanocortins afford cardioprotection in conditions of experimental myocardial ischemia/reperfusion, with involvement of the janus kinases (JAK), extracellular signal-regulated kinases (ERK) and signal transducers and activators of transcription (STAT) signalings. We investigated the influence of the melanocortin analog [Nle(4), D-Phe(7)]α-melanocyte-stimulating hormone (NDP-α-MSH) on short-term detrimental responses to cardiac arrest (CA) induced in rats by intravenous (i.v.) administration of potassium chloride, followed by cardiopulmonary resuscitation (CPR) plus epinephrine treatment. In CA/CPR rats i.v. treated with epinephrine (0.1 mg/kg) and returned to spontaneous circulation (48%) we recorded low values of mean arterial pressure (MAP) and heart rate (HR), alteration of hemogasanalysis parameters, left ventricle low expression of the cardioprotective transcription factors pJAK2 and pTyr-STAT3 (JAK-dependent), increased oxidative stress, up-regulation of the inflammatory mediators tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and down-regulation of the anti-inflammatory cytokine IL-10, as assessed at 1h and 3h after CPR. On the other hand, i.v. treatment during CPR with epinephrine plus NDP-α-MSH (340 μg/kg) almost completely restored the basal conditions of MAP and HR, reversed metabolic acidosis, induced left ventricle up-regulation of pJAK2, pTyr-STAT3 and IL-10, attenuated oxidative stress, down-regulated TNF-α and IL-6 levels, and improved survival rate by 81%. CA/CPR plus epinephrine alone or in combination with NDP-α-MSH did not affect left ventricle pSer-STAT3 (ERK1/2-dependent) and pERK1/2 levels. These results indicate that melanocortins improve return to spontaneous circulation, reverse metabolic acidosis, and inhibit heart oxidative stress and inflammatory cascade triggered by CA/CPR, likely via activation of the JAK/STAT signaling pathway.

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“…Rodent models of cardiac arrest followed by cardiopulmonary resuscitation have exhibited improved neurological performance and decreased neuronal damage with argon postconditioning [7,8,9]. Argon postconditioning was also neuroprotective in stroke models (middle cerebral artery occlusion) [10,11] and in vitro models of cerebral ischaemia and traumatic brain injury [12,13,14].…”

Section: Introductionmentioning

confidence: 99%

Argon Preconditioning Protects Airway Epithelial Cells against Hydrogen Peroxide-Induced Oxidative Stress

Hafner

Soto-Gonzalez

et al. 2016

Eur Surg Res

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Background: Oxidative stress is the predominant pathogenic mechanism of ischaemia-reperfusion (IR) injury. The noble gas argon has been shown to alleviate oxidative stress-related myocardial and cerebral injury. The risk of lung IR injury is increased in some major surgeries, reducing clinical outcome. However, no study has examined the lung-protective efficacy of argon preconditioning. The present study investigated the protective effects of argon preconditioning on airway epithelial cells exposed to hydrogen peroxide (H₂O₂) to induce oxidative stress. Methods: A549 airway epithelial cells were treated with a cytotoxic concentration of H₂O₂ after exposure to standard air or 30 or 50% argon/21% oxygen/5% carbon dioxide/rest nitrogen for 30, 45 or 180 min. Cells were stained with annexin V/propidium iodide, and apoptosis was evaluated by fluorescence-activated cell sorting. Protective signalling pathways activated by argon exposure were identified by Western blot analysis for phosphorylated candidate molecules of the mitogen-activated protein kinase and protein kinase B (Akt) pathways. Results: Preconditioning with 50% argon for 30, 45 and 180 min and 30% argon for 180 min caused significant protection of A549 cells against H₂O₂-induced apoptosis, with increases in cellular viability of 5-47% (p < 0.0001). A small adverse effect was also observed, which presented as a 12-15% increase in cellular necrosis in argon-treated groups. Argon exposure resulted in early activation of c-Jun N-terminal kinase (JNK) and p38, peaking 10- 30 min after the start of preconditioning, and delayed activation of the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway, peaking after 60-90 min. Conclusions: Argon preconditioning protects airway epithelial cells from H₂O₂-induced apoptotic cell death. Argon activates the JNK, p38, and ERK1/2 pathways, but not the Akt pathway. The cytoprotective properties of argon suggest possible prophylactic applications in surgery-related IR injury of the lungs.

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Dose dependent neuroprotection of the noble gas argon after cardiac arrest in rats is not mediated by KATP—Channel opening

Cited by 46 publications

References 31 publications

Argon: Systematic Review on Neuro- and Organoprotective Properties of an “Inert” Gas

Argon: Systematic Review on Neuro- and Organoprotective Properties of an “Inert” Gas

Protective effects of the melanocortin analog NDP-α-MSH in rats undergoing cardiac arrest

Argon Preconditioning Protects Airway Epithelial Cells against Hydrogen Peroxide-Induced Oxidative Stress

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