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Br J Anaesth. 2019 Jul;123(1):60-73. doi: 10.1016/j.bja.2019.02.032. Epub 2019 May 21.

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

Author information

1
Anaesthetics, Pain Medicine and Intensive Care Section, Department of Surgery and Cancer, UK; Royal British Legion Centre for Blast Injury Studies, Department of Bioengineering, Imperial College London, UK; Charing Cross Hospital Intensive Care Unit, Critical Care Directorate, Imperial College Healthcare NHS Trust, London, UK.
2
Department of Anaesthesiology, Medical Centre of Johannes Gutenberg University, Mainz, Germany.
3
Anaesthetics, Pain Medicine and Intensive Care Section, Department of Surgery and Cancer, UK.
4
Mouse Behavioural Outcome Unit, Focus Program Translational Neurosciences, Johannes Gutenberg University, Mainz, Germany.
5
Department of Life Sciences, Imperial College London, UK; Department of Anaesthetics, Royal Berkshire Hospital NHS Foundation Trust, Reading, UK.
6
Department of Life Sciences, Imperial College London, UK.
7
Department of Anaesthesiology, Medical Centre of Johannes Gutenberg University, Mainz, Germany. Electronic address: thal@uni-mainz.de.
8
Anaesthetics, Pain Medicine and Intensive Care Section, Department of Surgery and Cancer, UK; Royal British Legion Centre for Blast Injury Studies, Department of Bioengineering, Imperial College London, UK. Electronic address: r.dickinson@imperial.ac.uk.

Abstract

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% O2) or control gas (75% N2:25% O2). 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.

KEYWORDS:

general anaesthesia; hippocampus; memory disorders; nerve degeneration; neuroinflammation; neuroprotection; traumatic brain injury

PMID:
31122738
DOI:
10.1016/j.bja.2019.02.032
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