• Rita Campos-Pires, Tobias Hirnet, Flavia Valeo, Bee Eng Ong, Konstantin Radyushkin, Jitka Aldhoun, Joanna Saville, Christopher J Edge, Nicholas P Franks, Serge C Thal, and Robert Dickinson.
• 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.
• Br J Anaesth. 2019 Jul 1; 123 (1): 60-73.

BackgroundXenon 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.MethodsC57BL/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.ResultsXenon 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.ConclusionsXenon 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.Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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