PDF(Pubmed)
Abstract：
Traumatic brain injury (TBI) is a major public health concern, particularly in adolescents who have a higher mortality and incidence of visual pathway injury compared to adult patients. Likewise, we have found disparities between adult and adolescent TBI outcomes in rodents. Most interestingly, adolescents suffer a prolonged apneic period immediately post-injury, leading to higher mortality; therefore, we implemented a brief oxygen exposure paradigm to circumvent this increased mortality. Adolescent male mice experienced a closed-head weight-drop TBI and were then exposed to 100% O2 until normal breathing returned or recovered in room air. We followed mice for 7 and 30 days and assessed their optokinetic response; retinal ganglion cell loss; axonal degeneration; glial reactivity; and retinal ER stress protein levels. O2 reduced adolescent mortality by 40%, improved post-injury visual acuity, and reduced axonal degeneration and gliosis in optical projection regions. ER stress protein expression was altered in injured mice, and mice given O2 utilized different ER stress pathways in a time-dependent manner. Finally, O2 exposure may be mediating these ER stress responses through regulation of the redox-sensitive ER folding protein ERO1α, which has been linked to a reduction in the toxic effects of free radicals in other animal models of ER stress.
摘要：
创伤性脑损伤（TBI）是一个主要的公共卫生问题，特别是在与成年患者相比，视觉通路损伤的死亡率和发生率较高的青少年中。同样，我们发现啮齿动物的成人和青少年TBI结局之间存在差异.最有趣的是，青少年在受伤后立即经历了长时间的呼吸暂停期，导致更高的死亡率；因此，我们实施了一个简短的氧暴露模式来规避死亡率的增加.青春期雄性小鼠经历了头部闭合的重量下降TBI，然后暴露于100％O2，直到正常呼吸恢复或在室内空气中恢复。我们跟踪小鼠7天和30天，并评估它们的视动反应；视网膜神经节细胞丢失；轴突变性；神经胶质反应性；和视网膜内质网应激蛋白水平。O2使青少年死亡率降低了40%，改善受伤后的视力，并减少光学投影区域的轴突变性和胶质增生。损伤小鼠的ER应激蛋白表达发生改变，给予O2的小鼠以时间依赖性方式利用不同的ER应激途径。最后,O2暴露可能通过调节氧化还原敏感的ER折叠蛋白ERO1α来介导这些ER应激反应，这与其他ER应激动物模型中自由基毒性作用的减少有关。
