Beneficial Properties of Argon After Experimental Subarachnoid Hemorrhage: Early Treatment Reduces Mortality and Influences Hippocampal Protein Expression*

Höllig, Anke; Weinandy, Agnieszka; Liu, Jingjin; Clusmann, Hans; Rossaint, Rolf; Coburn, Mark

doi:10.1097/ccm.0000000000001561

Cited by 39 publications

(38 citation statements)

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“…In the initial trial design, a 24-h clinical evaluation using an 18- and 28-point scoring system was included. After the negative results in a similar study with argon, where we observed no difference in neurologic function in the acute phase ( 26 ), no short-term neurological evaluation was done in this trial.…”

Section: Methodsmentioning

confidence: 84%

“…SAH was induced by the polypropylene monofilament perforation technique initially described by Bederson et al and modified by Veelken et al ( 24 , 25 ). The procedure was performed as previously described ( 26 ). After exposing the left common carotid artery, the left internal carotid artery (ICA) was identified and a 3–0 polypropylene suture with a diameter ranging from 200 to 250 µm (Prolene suture, Ethicon Inc., Somerville, NJ, USA) was advanced intravascularly.…”

Section: Methodsmentioning

confidence: 99%

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Xenon Reduces Neuronal Hippocampal Damage and Alters the Pattern of Microglial Activation after Experimental Subarachnoid Hemorrhage: A Randomized Controlled Animal Trial

et al. 2017

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ObjectiveThe neuroprotective properties of the noble gas xenon have already been demonstrated using a variety of injury models. Here, we examine for the first time xenon’s possible effect in attenuating early brain injury (EBI) and its influence on posthemorrhagic microglial neuroinflammation in an in vivo rat model of subarachnoid hemorrhage (SAH).MethodsSprague-Dawley rats (n = 22) were randomly assigned to receive either Sham surgery (n = 9; divided into two groups) or SAH induction via endovascular perforation (n = 13, divided into two groups). Of those randomized for SAH, 7 animals were postoperatively ventilated with 50 vol% oxygen/50 vol% xenon for 1 h and 6 received 50 vol% oxygen/50 vol% nitrogen (control). The animals were sacrificed 24 h after SAH. Of each animal, a cerebral coronal section (−3.60 mm from bregma) was selected for assessment of histological damage 24 h after SAH. A 5-point neurohistopathological severity score was applied to assess neuronal cell damage in H&E and NeuN stained sections in a total of four predefined anatomical regions of interest. Microglial activation was evaluated by a software-assisted cell count of Iba-1 stained slices in three cortical regions of interest.ResultsA diffuse cellular damage was apparent in all regions of the ipsilateral hippocampus 24 h after SAH. Xenon-treated animals presented with a milder damage after SAH. This effect was found to be particularly pronounced in the medial regions of the hippocampus, CA3 (p = 0.040), and dentate gyrus (DG p = 0.040). However, for the CA1 and CA2 regions, there were no statistical differences in neuronal damage according to our histological scoring. A cell count of activated microglia was lower in the cortex of xenon-treated animals. This difference was especially apparent in the left piriform cortex (p = 0.017).ConclusionIn animals treated with 50 vol% xenon (for 1 h) after SAH, a less pronounced neuronal damage was observed for the ipsilateral hippocampal regions CA3 and DG, when compared to the control group. In xenon-treated animals, a lower microglial cell count was observed suggesting an immunomodulatory effect generated by xenon. As for now, these results cannot be generalized as only some hippocampal regions are affected. Future studies should assess the time and localization dependency of xenon’s beneficial properties after SAH.

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Section: Methodsmentioning

confidence: 84%

Section: Methodsmentioning

confidence: 99%

Xenon Reduces Neuronal Hippocampal Damage and Alters the Pattern of Microglial Activation after Experimental Subarachnoid Hemorrhage: A Randomized Controlled Animal Trial

et al. 2017

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“…Notably, the reported functional and histopathological neuroprotective effect in other traumatic, hypoxic and ischemic brain injury models has also been demonstrated in normothermic conditions 112627282930. A neuroprotective effect of noble gases can therefore not be explained by an augmented protective effect of hypothermia alone.…”

Section: Discussionmentioning

confidence: 92%

A porcine ex vivo lung perfusion model with maximal argon exposure to attenuate ischemia-reperfusion injury

et al. 2017

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Argon (Ar) is a noble gas with known organoprotective effects in rodents and in vitro models. In a previous study we failed to find a postconditioning effect of Ar during ex vivo lung perfusion (EVLP) on warm-ischemic injury in a porcine model. In this study, we further investigated a prolonged exposure to Ar to decrease cold ischemia-reperfusion injury after lung transplantation in a porcine model with EVLP assessment. Domestic pigs (n = 6/group) were pre-conditioned for 6 hours with 21% O2 and 79% N2 (CONTR) or 79% Ar (ARG). Subsequently, lungs were cold flushed and stored inflated on ice for 18 hours inflated with the same gas mixtures. Next, lungs were perfused for 4 hours on EVLP (acellular) while ventilated with 12% O2 and 88% N2 (CONTR group) or 88% Ar (ARG group). The perfusate was saturated with the same gas mixture but with the addition of CO2 to an end-tidal CO2 of 35-45 mmHg. The saturated perfusate was drained and lungs were perfused with whole blood for an additional 2 hours on EVLP. Evaluation at the end of EVLP did not show significant effects on physiologic parameters by prolonged exposure to Ar. Also wet-to-dry weight ratio did not improve in the ARG group. Although in other organ systems protective effects of Ar have been shown, we did not detect beneficial effects of a high concentration of Ar on cold pulmonary ischemia-reperfusion injury in a porcine lung model after prolonged exposure to Ar in this porcine model with EVLP assessment.

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“…Höllig et al [28] recently published the results of a new model, inducing brain injury by subarachnoid hemorrhage in rats. One hour after an intracranial endovascular perforation procedure, animals received argon 50% (50% O 2 ).…”

Section: Argon As a Neuroprotective Gaseous Molecule In Various Momentioning

confidence: 99%

“…After induction of subarachnoid hemorrhage (SAH) in rats, Höllig et al [28] performed Western blot analysis for HO-1 and HIF-1α protein of hippocampal tissue at different time points. The results are difficult to interpret; while argon treatment reduced HO-1 protein expression at 6 h after SAH, HO-1 was ultimately induced at 24 h. Furthermore, HIF-1α protein expression was significantly increased only after 24 h due to argon inhalation, while both proteins failed to show any elevated expressions at 72 h post injury.…”

Section: Intracellular Pathways Displaying Argon-mediated Neuropromentioning

confidence: 99%

The Molecular Pathway of Argon-Mediated Neuroprotection

Ulbrich

Goebel

2016

IJMS

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The noble gas argon has attracted increasing attention in recent years, especially because of its neuroprotective properties. In a variety of models, ranging from oxygen-glucose deprivation in cell culture to complex models of mid-cerebral artery occlusion, subarachnoid hemorrhage or retinal ischemia-reperfusion injury in animals, argon administration after individual injury demonstrated favorable effects, particularly increased cell survival and even improved neuronal function. As an inert molecule, argon did not show signs of adverse effects in the in vitro and in vivo model used, while being comparably cheap and easy to apply. However, the molecular mechanism by which argon is able to exert its protective and beneficial characteristics remains unclear. Although there are many pieces missing to complete the signaling pathway throughout the cell, it is the aim of this review to summarize the known parts of the molecular pathways and to combine them to provide a clear insight into the cellular pathway, starting with the receptors that may be involved in mediating argons effects and ending with the translational response.

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Beneficial Properties of Argon After Experimental Subarachnoid Hemorrhage: Early Treatment Reduces Mortality and Influences Hippocampal Protein Expression*

Cited by 39 publications

References 38 publications

Xenon Reduces Neuronal Hippocampal Damage and Alters the Pattern of Microglial Activation after Experimental Subarachnoid Hemorrhage: A Randomized Controlled Animal Trial

Xenon Reduces Neuronal Hippocampal Damage and Alters the Pattern of Microglial Activation after Experimental Subarachnoid Hemorrhage: A Randomized Controlled Animal Trial

A porcine ex vivo lung perfusion model with maximal argon exposure to attenuate ischemia-reperfusion injury

The Molecular Pathway of Argon-Mediated Neuroprotection

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