Prevention of neurotoxicity in hypoxic cortical neurons by the noble gas xenon

Petzelt, Christian; Blom, Per; Schmehl, W. R.; Müller, Jana; Kox, Wolfgang J.

doi:10.1016/s0024-3205(02)02439-6

Cited by 84 publications

(58 citation statements)

References 37 publications

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“…In addition, post-injury treatment with xenon 2 hours after a HI insult was also shown to be neuroprotective; again this effect was most marked in the CA1 region of the hippocampus. The neuroprotection afforded by xenon preconditioning and post-injury treatment in the organotypic hippocampal slice model, corroborated previous data from a variety of other in vivo and in vitro studies (18)(19)(20)(21), hence validating the use of this model for further studies of xenon neuroprotection.…”

Section: Discussionsupporting

confidence: 84%

“…Xenon, an NMDA receptor antagonist, has been shown to be neuroprotective in several paradigms of neuronal injury in both in vitro and in vivo models (18)(19)(20)(21). In vitro models, it offers the ability to strictly control the microenvironment and easily quantify cell death; however the major disadvantage is a loss of synaptic connections.…”

Section: Discussionmentioning

confidence: 99%

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Xenon Confers Neuroprotection in Organotypic Hippocampal Slice Cultures

Lan¹,

Sodha²,

Wang³

et al. 2016

J Anesth Perioper Med

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Background: The present study sought to establish the use of a novel model of cerebral ischaemia in which to investigate the neuroprotective effects of xenon based on organotypic hippocampal slice cultures. Methods: Organotypic hippocampal slices, derived from 7-10 days post-natal C57B16 mouse pups, were placed and cultured for 10-14 days on membranous inserts. Neuronal injury of cultures was provoked with media deprived with oxygen and glucose (OGD) for 2 hours. Cultures were exposed to 25% xenon or 50% xenon and 20% oxygen and 5% carbon dioxide (CO2) balanced with nitrogen (N2) 24 hours before OGD insult (preconditioning) for 2 hours or 75% xenon and 5% CO2 balanced with oxygen 4 hours after OGD for 2 hours. Cell death was quantified by assessment of propidium iodide (PI) uptake before and after OGD up to 72 hours in the CA1 and the dentate gyrus (DG) of the hippocampus. Results: Xenon preconditioning at concentrations of 25% and 50% resulted in a significant reduction in PI uptake in the CA1 region of the hippocampus compared with the control group (P<0.01). The effect was less pronounced in the DG region with xenon only at a concentration of 25% (P<0.05). Xenon 75% treatment 4 hours postinsult significantly attenuated cell death in both the DG and CA1 areas of the hippocampus. Conclusions: This study corroborated previous data to confirm that xenon is a potent neuroprotectant, and advocated its potential for future use in specific clinical settings.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Xenon Confers Neuroprotection in Organotypic Hippocampal Slice Cultures

Lan¹,

Sodha²,

Wang³

et al. 2016

J Anesth Perioper Med

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“…Xenon (Xe), a noble gas with anesthetic properties, has shown great promise as a neuroprotectant in both in vitro and in vivo experimental studies, especially when combined with deliberate cooling (Dingley et al, 2006;Hobbs et al, 2008a;Ma et al, 2005;Ma et al, 2002;Ma et al, 2003;Martin et al, 2007;Petzelt et al, 2003). Xenon is also attractive in this role because of its lack of chemical reactivity and lack of clinical side effects (Dingley et al, 2001;Marx et al, 1997;Preckel et al, 2004;Rossaint et al, 2003), rapid reversibility, and lack of fetotoxicity (Burov et al, 2002;Lane et al, 1980).…”

Section: Introductionmentioning

confidence: 99%

Cooling Combined with Immediate or Delayed Xenon Inhalation Provides Equivalent Long-Term Neuroprotection after Neonatal Hypoxia—Ischemia

Thoresen

Hobbs

Wood

et al. 2009

J Cereb Blood Flow Metab

151

117

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Hypothermia (HT) improves outcome after neonatal hypoxia-ischemia. Combination therapy may extend neuroprotection. The noble anesthetic gas xenon (Xe) has an excellent safety profile. We have shown earlier that 3 h of 50% Xe plus HT (321C) additively gives more protection (72%) than either alone (HT = 31.1%, Xe = 10.2%). Factors limiting clinical use include high-cost and specialist administration requirements. Thus, combinations of 1 h of 50% Xe were administered concurrently for either the first (1 h Immediate Xe) or last (1 h Delayed Xe) of 3 h of posthypoxic-ischemic HT as compared with 3 h of 50%Xe/HT to investigate how brief Xe exposure with a delay would affect efficacy. An established neonatal rat hypoxia-ischemia model was used. Serial functional neurologic testing into adulthood was performed, followed by neuropathological examination. Xenon with HT was more effective with longer Xe duration (3 h versus 1 h) (P = 0.015). However, 1 h Xe/3 h HT resulted in better neuroprotection than 3 h HT alone (P = 0.03), this significant effect was also present with 1 h Xe after a 2-h delay. One (immediate or with a delay) or 3 h Xe also significantly improved motor function (P = 0.024). Females had significantly better motor scores than males, but no sex-dependent difference in pathology results. The neuroprotection of short, delayed Xe treatment would allow transport to specialist facilities to receive Xe.

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“…The decision to explore this with the noble anaesthetic gas xenon is predicated by its very rapid onset and recovery characteristics, its lack of side effects Sanders et al, 2005) and the recent demonstration of its neuroprotective potential in both in vitro and in vivo models of acute neuronal injury (Ma et al, , 2003aWilhelm et al, 2002;Petzelt et al, 2003;Homi et al, 2003). Thus, we have investigated whether xenon is capable of preconditioning using a series of models from an in vitro glial-neuronal cell coculture system, through a hippocampal slice culture preparation, to an in vivo neonatal rat model.…”

Section: Introductionmentioning

confidence: 99%

Xenon Preconditioning Reduces Brain Damage from Neonatal Asphyxia in Rats

Hossain

Pettet

et al. 2006

J Cereb Blood Flow Metab

166

111

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Xenon attenuates on-going neuronal injury in both in vitro and in vivo models of hypoxic-ischaemic injury when administered during and after the insult. In the present study, we sought to investigate whether the neuroprotective efficacy of xenon can be observed when administered before an insult, referred to as 'preconditioning'. In a neuronal-glial cell coculture, preexposure to xenon for 2 h caused a concentration-dependent reduction of lactate dehydrogenase release from cells deprived of oxygen and glucose 24 h later; xenon's preconditioning effect was abolished by cycloheximide, a protein synthesis inhibitor. Preconditioning with xenon decreased propidium iodide staining in a hippocampal slice culture model subjected to oxygen and glucose deprivation. In an in vivo model of neonatal asphyxia involving hypoxic-ischaemic injury to 7-day-old rats, preconditioning with xenon reduced infarction size when assessed 7 days after injury. Furthermore, a sustained improvement in neurologic function was also evident 30 days after injury. Phosphorylated cAMP (cyclic adenosine 3 0 ,5 0 -monophosphate)-response element binding protein (pCREB) was increased by xenon exposure. Also, the prosurvival proteins Bcl-2 and brain-derived neurotrophic factor were upregulated by xenon treatment. These studies provide evidence for xenon's preconditioning effect, which might be caused by a pCREB-regulated synthesis of proteins that promote survival against neuronal injury.

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Prevention of neurotoxicity in hypoxic cortical neurons by the noble gas xenon

Cited by 84 publications

References 37 publications

Xenon Confers Neuroprotection in Organotypic Hippocampal Slice Cultures

Xenon Confers Neuroprotection in Organotypic Hippocampal Slice Cultures

Cooling Combined with Immediate or Delayed Xenon Inhalation Provides Equivalent Long-Term Neuroprotection after Neonatal Hypoxia—Ischemia

Xenon Preconditioning Reduces Brain Damage from Neonatal Asphyxia in Rats

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