Xenon improves neurologic outcome and reduces secondary injury following trauma in an in vivo model of traumatic brain injury
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Objectives: To determine the neuroprotective efficacy of the inert gas xenon following traumatic brain injury and to determine whether application of xenon has a clinically relevant therapeutic time window.
Design: Controlled animal study.
Setting: University research laboratory.
Subjects: Male C57BL/6N mice (n = 196).
Interventions: Seventy-five percent xenon, 50% xenon, or 30% xenon, with 25% oxygen (balance nitrogen) treatment following mechanical brain lesion by controlled cortical impact.
Measurements and Main Results: Outcome following trauma was measured using 1) functional neurologic outcome score, 2) histological measurement of contusion volume, and 3) analysis of locomotor function and gait. Our study shows that xenon treatment improves outcome following traumatic brain injury. Neurologic outcome scores were significantly (p < 0.05) better in xenon-treated groups in the early phase (24 hr) and up to 4 days after injury. Contusion volume was significantly (p < 0.05) reduced in the xenon-treated groups. Xenon treatment significantly (p < 0.05) reduced contusion volume when xenon was given 15 minutes after injury or when treatment was delayed 1 or 3 hours after injury. Neurologic outcome was significantly (p < 0.05) improved when xenon treatment was given 15 minutes or 1 hour after injury. Improvements in locomotor function (p < 0.05) were observed in the xenon-treated group, 1 month after trauma.
Conclusions: These results show for the first time that xenon improves neurologic outcome and reduces contusion volume following traumatic brain injury in mice. In this model, xenon application has a therapeutic time window of up to at least 3 hours. These findings support the idea that xenon may be of benefit as a neuroprotective treatment in patients with brain trauma.
Design: Controlled animal study.
Setting: University research laboratory.
Subjects: Male C57BL/6N mice (n = 196).
Interventions: Seventy-five percent xenon, 50% xenon, or 30% xenon, with 25% oxygen (balance nitrogen) treatment following mechanical brain lesion by controlled cortical impact.
Measurements and Main Results: Outcome following trauma was measured using 1) functional neurologic outcome score, 2) histological measurement of contusion volume, and 3) analysis of locomotor function and gait. Our study shows that xenon treatment improves outcome following traumatic brain injury. Neurologic outcome scores were significantly (p < 0.05) better in xenon-treated groups in the early phase (24 hr) and up to 4 days after injury. Contusion volume was significantly (p < 0.05) reduced in the xenon-treated groups. Xenon treatment significantly (p < 0.05) reduced contusion volume when xenon was given 15 minutes after injury or when treatment was delayed 1 or 3 hours after injury. Neurologic outcome was significantly (p < 0.05) improved when xenon treatment was given 15 minutes or 1 hour after injury. Improvements in locomotor function (p < 0.05) were observed in the xenon-treated group, 1 month after trauma.
Conclusions: These results show for the first time that xenon improves neurologic outcome and reduces contusion volume following traumatic brain injury in mice. In this model, xenon application has a therapeutic time window of up to at least 3 hours. These findings support the idea that xenon may be of benefit as a neuroprotective treatment in patients with brain trauma.
Date Issued
2015-01-01
Date Acceptance
2015-01-01
Citation
Critical Care Medicine, 2015, 43 (1), pp.149-158
ISSN
1530-0293
Publisher
Lippincott, Williams & Wilkins
Start Page
149
End Page
158
Journal / Book Title
Critical Care Medicine
Volume
43
Issue
1
Copyright Statement
This is not the final version of record, which can be found at https://dx.doi.org/10.1097/CCM.0000000000000624
Sponsor
European Society of Anaesthesiology
Medical Research Council (MRC)
British Journal of Anaesthesia
Royal Centre for Defence Medicine
Medical Research Council (MRC)
Identifier
https://journals.lww.com/ccmjournal/Fulltext/2015/01000/Xenon_Improves_Neurologic_Outcome_and_Reduces.18.aspx
Grant Number
N/A
MC_PC_13064
BJA/RCoA Grants NIAA Round 2
20120229-DMSRASG/Xenon
MC_PC_12015
Subjects
Science & Technology
Life Sciences & Biomedicine
Critical Care Medicine
General & Internal Medicine
brain injury
head trauma
inert gases
neuroprotection
xenon
D-ASPARTATE RECEPTOR
CONTROLLED CORTICAL IMPACT
CLOSED-HEAD INJURY
COMPETITIVE-INHIBITION
GLYCINE SITE
INTRACEREBRAL-HEMORRHAGE
INTRACRANIAL-PRESSURE
COGNITIVE DEFICITS
GAIT ABNORMALITIES
POTASSIUM CHANNELS
Publication Status
Published
Date Publish Online
2015-01-01