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

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Title: Xenon improves long-term cognitive function, reduces neuronal loss and chronic neuroinflammation, and improves survival after traumatic brain injury in mice
Authors: Campos-Pires, R
Hirnet, T
Valeo, F
Ong, BE
Radyushkin, K
Aldhoun, J
Saville, J
Edge, C
Franks, N
Thal, S
Dickinson, R
Item Type: Journal Article
Abstract: Background.Xenon is a noble gas with neuroprotective properties. We previously showed that xenon improves short and long-term outcomes in young adult mice after controlled cortical impact (CCI). This is a follow-up study investigating xenon’s effect on very long-term outcome and survival. Methods.C57BL/6N (n=72) young adult male mice received single CCI or sham surgery and were treated with either xenon (75%Xe:25%O2) or control gas (75% N2:25%O2). The outcomes used were: 1) 24-hour lesion volume and neurological outcome score; 2)contextual fear-conditioning at 2 weeks and 20 months; 3) corpus callosum white matter quantification; 4) immunohistological assessment of neuroinflammation and neuronal loss; 5) long-term survival. Results.Xenon treatment significantly reduced secondary injury development (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 reducedwhite matter loss in the contralateral corpus callosum and neuronal loss in the contralateral hippocampal CA1 andDG 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 to untreated animals up to 12 months after injury.Conclusions.These results show that 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.
Issue Date: Jul-2019
Date of Acceptance: 23-Feb-2019
URI: http://hdl.handle.net/10044/1/68070
DOI: https://doi.org/10.1016/j.bja.2019.02.032
ISSN: 1471-6771
Publisher: Elsevier
Start Page: 60
End Page: 73
Journal / Book Title: British Journal of Anaesthesia
Volume: 123
Issue: 1
Copyright Statement: © 2019 The Author(s). Published by Elsevier Ltd on behalf of British Journal of Anaesthesia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/ )
Sponsor/Funder: Royal Centre for Defence Medicine
British Journal of Anaesthesia
European Society of Anaesthesiology
Medical Research Council (MRC)
Medical Research Council (MRC)
The Gas Safety Trust
Carburos Metalicos S.E.C.M.S.A
Royal Centre for Defence Medicine
The Royal British Legion
The Royal British Legion
Funder's Grant Number: 20120229-DMSRASG/Xenon
BJA/RCoA Grants NIAA Round 2
N/A
MC_PC_13064
MR/N027736/1
WSSA_P64107
N/A
1012/4
Centre for Blast Injury Studie
Keywords: Science & Technology
Life Sciences & Biomedicine
Anesthesiology
hippocampus
general anaesthesia
memory disorders
nerve degeneration
neuroinflammation
neuroprotection
traumatic brain injury
D-ASPARTATE RECEPTOR
WHITE-MATTER DAMAGE
COMPETITIVE-INHIBITION
INHALED XENON
BUPRENORPHINE
HYPOPITUITARISM
EPIDEMIOLOGY
HYPOTHERMIA
ANALGESIA
PATHOLOGY
general anaesthesia
hippocampus
memory disorders
nerve degeneration
neuroinflammation
neuroprotection
traumatic brain injury
Animals
Brain
Brain Injuries, Traumatic
Chronic Disease
Cognition
Cognition Disorders
Disease Models, Animal
Follow-Up Studies
Inflammation
Male
Mice
Mice, Inbred C57BL
Neurons
Neuroprotective Agents
Survival Analysis
Xenon
Brain
Neurons
Animals
Mice, Inbred C57BL
Mice
Disease Models, Animal
Chronic Disease
Inflammation
Xenon
Neuroprotective Agents
Survival Analysis
Follow-Up Studies
Cognition
Cognition Disorders
Male
Brain Injuries, Traumatic
1103 Clinical Sciences
Anesthesiology
Publication Status: Published
Open Access location: http://10.0.3.248/j.bja.2019.02.032
Online Publication Date: 2019-05-21
Appears in Collections:Division of Surgery
Faculty of Medicine
Faculty of Natural Sciences



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