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Xenon treatment after severe traumatic brain injury improves locomotor outcome, reduces acute neuronal loss and enhances early beneficial neuroinflammation: a randomized, blinded, controlled animal study

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Title: Xenon treatment after severe traumatic brain injury improves locomotor outcome, reduces acute neuronal loss and enhances early beneficial neuroinflammation: a randomized, blinded, controlled animal study
Authors: Campos-Pires, R
Onggradito, H
Ujvari, E
Karimi, S
Valeo, F
Aldhoun, J
Edge, C
Franks, N
Dickinson, R
Item Type: Journal Article
Abstract: Background Traumatic brain injury (TBI) is a major cause of morbidity and mortality, but there are no clinically proven treatments that specifically target neuronal loss and secondary injury development following TBI. In this study, we evaluate the effect of xenon treatment on functional outcome, lesion volume, neuronal loss and neuroinflammation after severe TBI in rats. Methods Young adult male Sprague Dawley rats were subjected to controlled cortical impact (CCI) brain trauma or sham surgery followed by treatment with either 50% xenon:25% oxygen balance nitrogen, or control gas 75% nitrogen:25% oxygen. Locomotor function was assessed using Catwalk-XT automated gait analysis at baseline and 24 h after injury. Histological outcomes were assessed following perfusion fixation at 15 min or 24 h after injury or sham procedure. Results Xenon treatment reduced lesion volume, reduced early locomotor deficits, and attenuated neuronal loss in clinically relevant cortical and subcortical areas. Xenon treatment resulted in significant increases in Iba1-positive microglia and GFAP-positive reactive astrocytes that was associated with neuronal preservation. Conclusions Our findings demonstrate that xenon improves functional outcome and reduces neuronal loss after brain trauma in rats. Neuronal preservation was associated with a xenon-induced enhancement of microglial cell numbers and astrocyte activation, consistent with a role for early beneficial neuroinflammation in xenon’s neuroprotective effect. These findings suggest that xenon may be a first-line clinical treatment for brain trauma.
Issue Date: 27-Nov-2020
Date of Acceptance: 1-Nov-2020
URI: http://hdl.handle.net/10044/1/84925
DOI: 10.1186/s13054-020-03373-9
ISSN: 1364-8535
Publisher: BioMed Central
Start Page: 1
End Page: 18
Journal / Book Title: Critical Care (UK)
Volume: 24
Copyright Statement: © The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativeco mmons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
Sponsor/Funder: Royal Centre for Defence Medicine
Medical Research Council (MRC)
The Gas Safety Trust
Wellcome Trust
Funder's Grant Number: 20120229-DMSRASG/Xenon
MR/N027736/1
WSSA_P64107
057279/Z/99/Z
Keywords: Acquired brain injury
Locomotor deficit
Neuroglia
Neuroinflammation
Neuroprotection
Neurotrauma
Noble gases
Xenon
Emergency & Critical Care Medicine
11 Medical and Health Sciences
Publication Status: Published
Article Number: 667
Online Publication Date: 2020-11-27
Appears in Collections:Department of Surgery and Cancer
Faculty of Natural Sciences



This item is licensed under a Creative Commons License Creative Commons