TY - JOUR
T1 - Argon Inhalation for 24 Hours After Onset of Permanent Focal Cerebral Ischemia in Rats Provides Neuroprotection and Improves Neurologic Outcome
AU - Ma, Shuang
AU - Chu, Dongmei
AU - Li, Litao
AU - Creed, Jennifer A.
AU - Ryang, Yu Mi
AU - Sheng, Huaxin
AU - Yang, Wei
AU - Warner, David S.
AU - Turner, Dennis A.
AU - Hoffmann, Ulrike
N1 - Funding Information:
1Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, Liao Ning, China. 2Multidisciplinary Neuroprotection Laboratories, Departments of Anesthesiology, Biomedical Engineering, Neurobiology, and Neurosurgery, Duke University, Durham, NC. 3Department of Pediatrics, The Fifth Central Hospital of Tianjin, Tianjin, China. 4Department of Neurology, Hebei General Hospital, Hebei Medical University, Shijiazhuang, China. 5Department of Neurosurgery, Klinikum rechts der Isar, TU Munich, Germany. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http;/journals.lww.com/ ccmjournal). Supported, in part, by a DREAM Award from the Department of Anesthesiology at Duke University Medical Center.
Funding Information:
Dr. Sheng’s institution received funding from the National Institutes of erebral ischemic stroke remains one of the most com-from the NIH. Dr. Yang received support for article research from depart-Health (NIH). Drs. Sheng and Turner received support for article research mon causes of death and disability worldwide. Despite mental funds. Dr. Hoffmann received support for article research from the Cextensive efforts to develop new treatment strategies, Department of Duke Anesthesiology DREAM award, and he disclosed timely reperfusion remains the only effective intervention for closed that they do not have any potential conflicts of interest.off-label product use of noble gas argon. The remaining authors have dis- ischemic stroke. Although reperfusion within a certain time For information regarding this article, E-mail: ulrike.hoffmann@duke.edu window can reduce infarct size and improve clinical outcome, Copyright © 2019 by the Society of Critical Care Medicine and Wolters “cerebral reperfusion injury” (1) can occur, exacerbating brain Kluwer Health, Inc. All Rights Reserved. injury. Unfortunately, only about 10% of stroke patients are DOI: 10.1097/CCM.0000000000003809 eligible for reperfusion attempts, but not all are successfully
Publisher Copyright:
© 2019 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - Objectives: We tested the hypothesis that prolonged inhalation of 70% argon for 24 hours after in vivo permanent or temporary stroke provides neuroprotection and improves neurologic outcome and overall recovery after 7 days. Design: Controlled, randomized, double-blinded laboratory study. Setting: Animal research laboratories. Subjects: Adult Wistar male rats (n = 110). Interventions: Rats were subjected to permanent or temporary focal cerebral ischemia via middle cerebral artery occlusion, followed by inhalation of 70% argon or nitrogen in 30% oxygen for 24 hours. On postoperative day 7, a 48-point neuroscore and histologic lesion size were assessed. Measurements and Main Results: After argon inhalation for 24 hours immediately following "severe permanent ischemia" induction, neurologic outcome (neuroscore, p = 0.034), overall recovery (body weight, p = 0.02), and infarct volume (total infarct volume, p = 0.0001; cortical infarct volume, p = 0.0003; subcortical infarct volume, p = 0.0001) were significantly improved. When 24-hour argon treatment was delayed for 2 hours after permanent stroke induction or until after postischemic reperfusion treatment, neurologic outcomes remained significantly improved (neuroscore, p = 0.043 and p = 0.014, respectively), as was overall recovery (body weight, p = 0.015), compared with nitrogen treatment. However, infarct volume and 7-day mortality were not significantly reduced when argon treatment was delayed. Conclusions: Neurologic outcome (neuroscore), overall recovery (body weight), and infarct volumes were significantly improved after 24-hour inhalation of 70% argon administered immediately after severe permanent stroke induction. Neurologic outcome and overall recovery were also significantly improved even when argon treatment was delayed for 2 hours or until after reperfusion.
AB - Objectives: We tested the hypothesis that prolonged inhalation of 70% argon for 24 hours after in vivo permanent or temporary stroke provides neuroprotection and improves neurologic outcome and overall recovery after 7 days. Design: Controlled, randomized, double-blinded laboratory study. Setting: Animal research laboratories. Subjects: Adult Wistar male rats (n = 110). Interventions: Rats were subjected to permanent or temporary focal cerebral ischemia via middle cerebral artery occlusion, followed by inhalation of 70% argon or nitrogen in 30% oxygen for 24 hours. On postoperative day 7, a 48-point neuroscore and histologic lesion size were assessed. Measurements and Main Results: After argon inhalation for 24 hours immediately following "severe permanent ischemia" induction, neurologic outcome (neuroscore, p = 0.034), overall recovery (body weight, p = 0.02), and infarct volume (total infarct volume, p = 0.0001; cortical infarct volume, p = 0.0003; subcortical infarct volume, p = 0.0001) were significantly improved. When 24-hour argon treatment was delayed for 2 hours after permanent stroke induction or until after postischemic reperfusion treatment, neurologic outcomes remained significantly improved (neuroscore, p = 0.043 and p = 0.014, respectively), as was overall recovery (body weight, p = 0.015), compared with nitrogen treatment. However, infarct volume and 7-day mortality were not significantly reduced when argon treatment was delayed. Conclusions: Neurologic outcome (neuroscore), overall recovery (body weight), and infarct volumes were significantly improved after 24-hour inhalation of 70% argon administered immediately after severe permanent stroke induction. Neurologic outcome and overall recovery were also significantly improved even when argon treatment was delayed for 2 hours or until after reperfusion.
KW - argon
KW - neuroprotection
KW - noble gases
KW - permanent cerebral ischemia
KW - rats
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U2 - 10.1097/CCM.0000000000003809
DO - 10.1097/CCM.0000000000003809
M3 - Article
C2 - 31094741
AN - SCOPUS:85069888545
SN - 0090-3493
VL - 47
SP - E693-E699
JO - Critical Care Medicine
JF - Critical Care Medicine
IS - 8
ER -