The neurocognitive impairments associated with mild traumatic brain injury (TBI) often resolve within 1–2 weeks; however, a subset of people exhibit persistent cognitive dysfunction for weeks to months after injury. The factors that contribute to these persistent deficits are unknown. One potential risk factor for worsened outcome after TBI is a history of stress experienced by a person early in life. Early life stress (ELS) includes maltreatment such as neglect, and interferes with the normal construction of cortical and hippocampal circuits. We hypothesized that a history of ELS contributes to persistent learning and memory dysfunction following a TBI. To explore this interaction, we modeled ELS by separating Sprague Dawley pups from their nursing mothers from post-natal days 2–14 for 3 h daily. At 2 months of age, male rats received sham surgery or mild to moderate parasagittal fluid-percussion brain injury. We found that the combination of ELS with TBI in adulthood impaired hippocampal-dependent learning, as assessed with contextual fear conditioning, the water maze task, and spatial working memory. Cortical atrophy was significantly exacerbated in TBI animals exposed to ELS compared with normal-reared TBI animals. Changes in corticosterone in response to restraint stress were prolonged in TBI animals that received ELS compared with TBI animals that were normally reared or sham animals that received ELS. Our findings indicate that ELS is a risk factor for worsened outcome after TBI, and results in persistent learning and memory deficits, worsened cortical pathology, and an exacerbation of the hormonal stress response.

中文翻译：

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早期生活压力加剧了创伤性脑损伤后的结果

与轻度创伤性脑损伤 (TBI) 相关的神经认知障碍通常会在 1-2 周内消退；然而，一部分人在受伤后的数周到数月内表现出持续的认知功能障碍。导致这些持续缺陷的因素尚不清楚。TBI 后结果恶化的一个潜在风险因素是一个人在生命早期经历的压力史。早期生活压力 (ELS) 包括忽视等虐待，并干扰皮质和海马回路的正常构建。我们假设 ELS 病史会导致 TBI 后持续的学习和记忆功能障碍。为了探索这种相互作用，我们通过将 Sprague Dawley 幼崽与产后第 2-14 天的哺乳母亲分开 3 小时来模拟 ELS。2个月大时，雄性大鼠接受了假手术或轻度至中度的矢状旁液敲击脑损伤。我们发现 ELS 与 TBI 的组合在成年期损害了海马依赖性学习，这是通过情境恐惧条件反射、水迷宫任务和空间工作记忆进行评估的。与正常饲养的 TBI 动物相比，暴露于 ELS 的 TBI 动物的皮质萎缩显着加剧。与正常饲养的 TBI 动物或接受 ELS 的假动物相比，接受 ELS 的 TBI 动物中皮质酮响应约束压力的变化延长。我们的研究结果表明，ELS 是 TBI 后结果恶化的风险因素，并导致持续的学习和记忆缺陷、皮质病理恶化和激素应激反应加剧。