Department of Surgery, Division of Trauma and Critical Care, Northwestern University, Chicago, IL, USA.
Department of Surgery, Division of Trauma and Critical Care, Northwestern University, Chicago, IL, USA.
Exp Neurol. 2021 Jul;341:113714. doi: 10.1016/j.expneurol.2021.113714. Epub 2021 Apr 5.
The CDC estimate that nearly 3 million Americans sustain a traumatic brain injury (TBI) each year. Even when medical comorbidities are accounted for, age is an independent risk factor for poor outcome after TBI. Nonetheless, few studies have examined the pathophysiology of age-linked biologic outcomes in TBI. We hypothesized that aged mice would demonstrate more severe neuropathology and greater functional deficits as compared to young adult mice after equivalent traumatic brain injuries. Young adult (14-week-old) and aged (80-week-old) C57BL/6 male mice underwent an open-head controlled cortical impact to induce TBI or a sham injury. At 30-days post-injury groups underwent behavioral phenotyping, magnetic resonance imaging, and histologic analyses. Contrary to our hypothesis, young adult TBI mice exhibited more severe neuropathology and greater loss of white matter connectivity as compared to aged mice after TBI. These findings correlated to differential functional outcomes in anxiety response, learning, and memory between young adult and aged mice after TBI. Although the mechanisms underlying this age-effect remain unclear, attenuated signs of secondary brain injury in aged TBI mice point towards different inflammatory and repair processes between age groups. These data suggest that age may need to be an a priori consideration in future clinical trial design.
美国疾病控制与预防中心估计，每年有近 300 万美国人遭受创伤性脑损伤（TBI）。即使考虑到合并的医学疾病，年龄也是 TBI 后预后不良的独立危险因素。然而，很少有研究检查 TBI 中与年龄相关的生物学结果的病理生理学。我们假设，与年轻成年小鼠相比，年老小鼠在遭受同等程度的创伤性脑损伤后，会表现出更严重的神经病理学和更大的功能缺陷。年轻成年（14 周龄）和年老（80 周龄）C57BL/6 雄性小鼠接受开颅控制性皮质撞击以诱导 TBI 或假损伤。在损伤后 30 天，各组进行行为表型、磁共振成像和组织学分析。与我们的假设相反，与年老小鼠相比，年轻成年 TBI 小鼠在 TBI 后表现出更严重的神经病理学和更大的白质连接丧失。这些发现与 TBI 后年轻成年和年老成年小鼠在焦虑反应、学习和记忆方面的功能结果差异相关。尽管这种年龄效应的机制尚不清楚，但年老 TBI 小鼠中继发性脑损伤的迹象减弱表明，不同年龄组之间的炎症和修复过程不同。这些数据表明，在未来的临床试验设计中，年龄可能需要作为一个先验考虑因素。
