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Argon Inhalation for 24 Hours After Onset of Permanent Focal Cerebral Ischemia in Rats Provides Neuroprotection and Improves Neurologic Outcome

Ma, Shuang MD1,2; Chu, Dongmei MD2,3; Li, Litao MD2,4; Creed, Jennifer A. MD, PhD2; Ryang, Yu-Mi MD, PhD5; Sheng, Huaxin MD2; Yang, Wei PhD2; Warner, David S. MD2; Turner, Dennis A. MA, MD2; Hoffmann, Ulrike MD, PhD2

doi: 10.1097/CCM.0000000000003809
Online Laboratory Investigations

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.

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.

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Supported, in part, by a DREAM Award from the Department of Anesthesiology at Duke University Medical Center.

Dr. Sheng’s institution received funding from the National Institutes of Health (NIH). Drs. Sheng and Turner received support for article research from the NIH. Dr. Yang received support for article research from departmental funds. Dr. Hoffmann received support for article research from the Department of Duke Anesthesiology DREAM award, and he disclosed off-label product use of noble gas argon. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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