Xenon Protects against Blast-Induced Traumatic Brain Injury in an <i>In Vitro</i> Model

Campos-Pires, Rita; Koziakova, Mariia; Yonis, Amina; Pau, Ashni; Macdonald, Warren; Harris, Katie; Edge, Christopher J.; Franks, Nicholas P.; Mahoney, Peter F.; Dickinson, Robert

doi:10.1089/neu.2017.5360

Cited by 31 publications

(20 citation statements)

References 50 publications

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“…Xenon has recently been shown to be effective in reducing white matter damage in humans after ischaemic brain injury resulting from out-of-hospital cardiac arrest 12 . Xenon is protective in in vitro models of brain trauma,13, 14, 15 but much less is known about its effects in brain trauma in vivo. We previously showed in an animal model that administration of xenon after TBI improves short-term (up to 4 days) and long-term outcomes (28 days) in mice 16 .…”

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confidence: 99%

Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice

Campos-Pires

Hirnet

Valeo³

et al. 2019

British Journal of Anaesthesia

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Background Xenon is a noble gas with neuroprotective properties that can improve short and long-term outcomes in young adult mice after controlled cortical impact. This follow-up study investigates the effects of xenon on very long-term outcomes and survival. Methods C57BL/6N young adult male mice ( n =72) received single controlled cortical impact or sham surgery and were treated with either xenon (75% Xe:25% O 2 ) or control gas (75% N 2 :25% O 2 ). Outcomes measured were: (i) 24 h lesion volume and neurological outcome score; (ii) contextual fear conditioning at 2 weeks and 20 months; (iii) corpus callosum white matter quantification; (iv) immunohistological assessment of neuroinflammation and neuronal loss; and (v) long-term survival. Results Xenon treatment significantly reduced secondary injury ( P <0.05), improved short-term vestibulomotor function ( P <0.01), and prevented development of very late-onset traumatic brain injury (TBI)-related memory deficits. Xenon treatment reduced white matter loss in the contralateral corpus callosum and neuronal loss in the contralateral hippocampal CA1 and dentate gyrus areas at 20 months. Xenon's long-term neuroprotective effects were associated with a significant ( P <0.05) reduction in neuroinflammation in multiple brain areas involved in associative memory, including reduction in reactive astrogliosis and microglial cell proliferation. Survival was improved significantly ( P <0.05) in xenon-treated animals compared with untreated animals up to 12 months after injury. Conclusions Xenon treatment after TBI results in very long-term improvements in clinically relevant outcomes and survival. Our findings support the idea that xenon treatment shortly after TBI may have long-term benefits in the treatment of brain trauma patients.

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confidence: 99%

Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice

Campos-Pires

Hirnet

Valeo³

et al. 2019

British Journal of Anaesthesia

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“…This preparation retains a variety of cell types (e.g. different types of neurones and glia) with cellular organisation and synaptic connectivity similar to in vivo ,34, 35 and is widely used as an intermediate between dissociated cell cultures and whole-animal models 20, 24, 26, 28, 36, 37, 38, 39, 40. We chose 30 min as the duration of OGD because we previously showed that this produced a reliable and robust injury 24 .…”

Section: Discussionmentioning

confidence: 99%

Noble gas neuroprotection: xenon and argon protect against hypoxic–ischaemic injury in rat hippocampus in vitro via distinct mechanisms

Koziakova

Harris

Edge

et al. 2019

British Journal of Anaesthesia

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Background: Noble gases may provide novel treatments for neurological injuries such as ischaemic and traumatic brain injury. Few studies have evaluated the complete series of noble gases under identical conditions in the same model. Methods: We used an in vitro model of hypoxiaeischaemia to evaluate the neuroprotective properties of the series of noble gases, helium, neon, argon, krypton, and xenon. Organotypic hippocampal brain slices from mice were subjected to oxygen-glucose deprivation, and injury was quantified using propidium iodide fluorescence. Results: Both xenon and argon were equally effective neuroprotectants, with 0.5 atm of xenon or argon reducing injury by 96% (P<0.0001), whereas helium, neon, and krypton were devoid of any protective effect. Neuroprotection by xenon, but not argon, was reversed by elevated glycine. Conclusions: Xenon and argon are equally effective as neuroprotectants against hypoxiaeischaemia in vitro, with both gases preventing injury development. Although xenon's neuroprotective effect may be mediated by inhibition of the Nmethyl-D-aspartate receptor at the glycine site, argon acts via a different mechanism. These findings may have important implications for their clinical use as neuroprotectants.

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“…In addition to quantifying cell injury in the slices over time, the tissue can be fixed at the end of the experiment for conventional immunohistochemistry 50 . We developed and evaluated the method using mouse hippocampal slices.…”

Section: Discussionmentioning

confidence: 99%

A Novel <em>In Vitro</em> Model of Blast Traumatic Brain Injury

Campos-Pires

Yonis

Macdonald

et al. 2018

JoVE

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Traumatic brain injury is a leading cause of death and disability in military and civilian populations. Blast traumatic brain injury results from the detonation of explosive devices, however, the mechanisms that underlie the brain damage resulting from blast overpressure exposure are not entirely understood and are believed to be unique to this type of brain injury. Preclinical models are crucial tools that contribute to better understand blast-induced brain injury. A novel in vitro blast TBI model was developed using an open-ended shock tube to simulate real-life open-field blast waves modelled by the Friedlander waveform. C57BL/6N mouse organotypic hippocampal slice cultures were exposed to single shock waves and the development of injury was characterized up to 72 h using propidium iodide, a well-established fluorescent marker of cell damage that only penetrates cells with compromised cellular membranes. Propidium iodide fluorescence was significantly higher in the slices exposed to a blast wave when compared with sham slices throughout the duration of the protocol. The brain tissue injury is very reproducible and proportional to the peak overpressure of the shock wave applied.

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Xenon Protects against Blast-Induced Traumatic Brain Injury in an In Vitro Model

Cited by 31 publications

References 50 publications

Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice

Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice

Noble gas neuroprotection: xenon and argon protect against hypoxic–ischaemic injury in rat hippocampus in vitro via distinct mechanisms

A Novel <em>In Vitro</em> Model of Blast Traumatic Brain Injury

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