Traumatic brain injury (TBI) is a serious health issue that causes long-term neurological disability, particularly in young adults, athletes and war veterans. Despite the use of different medications or surgical procedures, no effective therapy is currently available to halt its pathogenesis. Here, we have undertaken a novel approach to reduce neuroinflammation and improve cognitive, social and locomotor behaviors in a mouse model of TBI. RNS60 is a physiologic saline solution containing oxygen nanobubbles that is generated by subjecting normal saline to Taylor-Couette-Poiseuille (TCP) flow under elevated oxygen pressure. Recently we have delineated that RNS60 inhibits the expression of proinflammatory molecules in glial cells via type 1A phosphatidylinositol-3 kinase (PI3K)-mediated upregulation of IκBα. In this study, we found that TBI decreased the level of IκBα and increased the activation of NF-κB in hippocampus and cortex as monitored by the upregulation of p-p65. However, intraperitoneal administration of RNS60 increased and/or restored the level of IκBα and inhibited the activation of NF-κB in hippocampus and cortex of TBI mice. Accordingly, RNS60 treatment decreased the activation of astrocytes and microglia and reduced neuronal apoptosis in the brain of TBI mice. RNS60 treatment also reduced vascular damage, attenuated blood-brain barrier leakage and decreased the size of lesion in the brain of TBI mice. Importantly, RNS60 treated mice showed significant improvements in memory, social behavior and locomotor activities while displaying reduction in depression-like behaviors. These results delineate a novel neuroprotective property of RNS60 and suggest its possible therapeutic use in TBI.

颅脑外伤（TBI）是严重的健康问题，会引起长期的神经功能障碍，尤其是在年轻人，运动员和退伍军人中。尽管使用了不同的药物或外科手术程序，但目前尚无有效的疗法来停止其发病机理。在这里，我们采取了一种新颖的方法来减少TBI小鼠模型中的神经炎症并改善认知，社交和运动行为。RNS60是一种含氧纳米气泡的生理盐水溶液，是通过在升高的氧气压力下使生理盐水经受Taylor-Couette-Poiseuille（TCP）流动产生的。最近，我们描述了RNS60通过1A型磷脂酰肌醇3激酶（PI3K）介导的IκBα上调抑制神经胶质细胞中促炎分子的表达。在这个研究中，我们发现，TBI可以通过上调p-p65来降低海马和皮质中IκBα的水平，并增加NF-κB的活化。然而，腹膜内施用RNS60增加和/或恢复了TBI小鼠海马和皮质中IκBα的水平并抑制了NF-κB的活化。因此，RNS60处理可降低TBI小鼠大脑中星形胶质细胞和小胶质细胞的活化并减少神经元凋亡。RNS60处理还减少了TBI小鼠大脑中的血管损伤，减弱了血脑屏障的泄漏并减小了病变的大小。重要的是，经RNS60处理的小鼠在记忆，社交行为和自发活动方面表现出显着改善，同时表现出抑郁样行为减少。