Differential neuropathology and functional outcome after equivalent traumatic brain injury in aged versus young adult mice.
Differential neuropathology and functional outcome after equivalent traumatic brain injury in aged versus young adult mice.
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DOI：
10.1016/j.expneurol.2021.113714
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发表时间：
2021-07
影响因子：
5.3
通讯作者：
Schwulst SJ
中科院分区：
文献类型：
--
作者：
Islam MBAR;Davis BT 4th;Kando MJ;Mao Q;Procissi D;Weiss C;Schwulst SJ
CDC估计，每年有近300万美国人遭受创伤性脑损伤（TBI）。即使考虑到合并症，年龄也是TBI预后不良的独立危险因素。尽管如此，很少有研究探讨TBI中与年龄相关的生物学结局的病理生理学。我们假设，老年小鼠将表现出更严重的神经病理学和更大的功能缺陷相比，年轻的成年小鼠后，等效的创伤性脑损伤。年轻成年（14周龄）和老年（80周龄）C57 BL/6雄性小鼠进行了开放式头部控制的皮质撞击，以诱导TBI或假损伤。在损伤后30天，对各组进行行为表型分析、磁共振成像和组织学分析。与我们的假设相反，年轻的成年TBI小鼠表现出更严重的神经病理学和更大的损失相比，老年小鼠TBI后的白色物质连接。这些发现与TBI后年轻成年小鼠和老年小鼠在焦虑反应、学习和记忆方面的不同功能结果相关。尽管这种年龄效应的机制尚不清楚，但老年TBI小鼠继发性脑损伤的减弱迹象表明年龄组之间存在不同的炎症和修复过程。这些数据表明，在未来的临床试验设计中，年龄可能需要作为先验考虑因素。
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.
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