González Torrecilla Sandra, Delbrel Alisée, Giacomino Laura, Meunier David, Sein Julien, Renaud Luc, Brige Pauline, Garrigue Philippe, Hak Jean Francois, Guillet Benjamin, Brunel Hervé, Farjot Géraldine, Brochier Thomas, Velly Lionel
Institut de Neurosciences de la Timone (INT), CNRS, Aix-Marseille Université, Marseille, France.
Medical School, Newcastle University, Newcastle upon Tyne, UK.
J Cereb Blood Flow Metab. 2025 Apr;45(4):643-654. doi: 10.1177/0271678X241297798. Epub 2024 Dec 4.
In the past decade, noble gases have emerged as highly promising neuroprotective agents. Previous studies have demonstrated the efficacy of argon neuroprotection in rodent models of cerebral ischemia. The objective of the present pre-clinical study was to confirm the neuroprotective effect of argon in a non-human primate model of endovascular ischemic stroke. Thirteen adult were subjected to a focal cerebral ischemia induced by a transient (90 min) middle cerebral artery occlusion (tMCAO). The monkeys were randomly allocated to a control group (n = 8) and an argon group (n = 5). Pre-mixed gas (40-60 oxygen-argon) was applied 30 min after the onset of tMCAO to 30 min after reperfusion. Infarct volumes were measured from the MRI scans conducted 1 hour and 1 month after the reperfusion. A clinical neurological assessment was performed 24 hours and 1 month after tMCAO. Our results show that Argon dramatically reduced ischemic core volume after ischemia compared to the control group with a long-lasting improvement of post-stroke infarct volume at 1 month. In addition, the neurological scale suggests a better prognosis in argon-treated animals without reaching the significance threshold. These pre-clinical results in gyrencephalic non-human primates support the potential use of this therapeutic approach for future clinical studies.
在过去十年中,稀有气体已成为极具前景的神经保护剂。先前的研究已证明氩气在脑缺血啮齿动物模型中的神经保护作用。本临床前研究的目的是在血管内缺血性中风的非人灵长类动物模型中证实氩气的神经保护作用。13只成年动物接受了短暂性(90分钟)大脑中动脉闭塞(tMCAO)诱导的局灶性脑缺血。这些猴子被随机分为对照组(n = 8)和氩气组(n = 5)。在tMCAO发作后30分钟至再灌注后30分钟应用预混气体(40 - 60氧气 - 氩气)。在再灌注后1小时和1个月进行的MRI扫描中测量梗死体积。在tMCAO后24小时和1个月进行临床神经学评估。我们的结果表明,与对照组相比,氩气在缺血后显著减少了缺血核心体积,并且在1个月时对中风后梗死体积有持久的改善。此外,神经学评分表明接受氩气治疗的动物预后较好,但未达到显著阈值。这些在脑回非人灵长类动物中的临床前结果支持了这种治疗方法在未来临床研究中的潜在应用。