Laboratory of Acute Brain Injury and Therapeutic Strategies, Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy.
Laboratory of Acute Brain Injury and Therapeutic Strategies, Department of Neuroscience, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy; School of Medicine and Surgery, University of Milan-Bicocca, Milan, Italy.
Br J Anaesth. 2021 Jan;126(1):256-264. doi: 10.1016/j.bja.2020.08.027. Epub 2020 Sep 22.
Whilst there has been progress in supportive treatment for traumatic brain injury (TBI), specific neuroprotective interventions are lacking. Models of ischaemic heart and brain injury show the therapeutic potential of argon gas, but it is still not known whether inhaled argon (iAr) is protective in TBI. We tested the effects of acute administration of iAr on brain oedema, tissue micro-environmental changes, neurological functions, and structural outcome in a mouse model of TBI.
Anaesthetised adult C57BL/6J mice were subjected to severe TBI by controlled cortical impact. Ten minutes after TBI, the mice were randomised to 24 h treatments with iAr 70%/O 30% or air (iCtr). Sensorimotor deficits were evaluated up to 6 weeks post-TBI by three independent tests. Cognitive function was evaluated by Barnes maze test at 4 weeks. MRI was done to examine brain oedema at 3 days and white matter damage at 5 weeks. Microglia/macrophages activation and functional commitment were evaluated at 1 week after TBI by immunohistochemistry.
iAr significantly accelerated sensorimotor recovery and improved cognitive deficits 1 month after TBI, with less white matter damage in the ipsilateral fimbria and body of the corpus callosum. Early changes underpinning protection included a reduction of pericontusional vasogenic oedema and of the inflammatory response. iAr significantly reduced microglial activation with increases in ramified cells and the M2-like marker YM1.
iAr accelerates recovery of sensorimotor function and improves cognitive and structural outcome 1 month after severe TBI in adult mice. Early effects include a reduction of brain oedema and neuroinflammation in the contused tissue.
尽管在创伤性脑损伤（TBI）的支持性治疗方面已经取得了进展，但仍缺乏特定的神经保护干预措施。缺血性心脏和大脑损伤模型显示出氩气的治疗潜力，但吸入氩气（iAr）是否对 TBI 具有保护作用仍不清楚。我们测试了急性给予 iAr 对 TBI 小鼠模型中脑水肿、组织微环境变化、神经功能和结构结果的影响。
麻醉的成年 C57BL/6J 小鼠通过皮质撞击控制法接受严重的 TBI。TBI 后 10 分钟，将小鼠随机分为 iAr 70%/O 30%或空气（iCtr）24 小时处理组。TBI 后最多 6 周通过三项独立的测试评估感觉运动缺陷。4 周时进行 Barnes 迷宫测试评估认知功能。MRI 用于检查 3 天的脑水肿和 5 周的白质损伤。通过免疫组织化学在 TBI 后 1 周评估小胶质细胞/巨噬细胞激活和功能承诺。
iAr 可显著加速 TBI 后 1 个月的感觉运动恢复并改善认知缺陷，同侧穹窿和胼胝体体部的白质损伤减少。保护的早期变化包括减少外伤性血管源性水肿和炎症反应。iAr 可显著减少小胶质细胞激活，增加分支细胞和 M2 样标志物 YM1。
iAr 可加速成年小鼠严重 TBI 后 1 个月的感觉运动功能恢复并改善认知和结构结果。早期影响包括减少挫伤组织中的脑水肿和神经炎症。
