BACKGROUND Traumatic brain injury (TBI) is among the most prevalent causes of cerebrovascular and neurological damage worldwide. To this end, tobacco smoke (TS) has been shown to promote vascular inflammation, neurovascular impairments, and risk of cerebrovascular and neurological disorders through oxidative stress (OS) stimuli targeting the blood-brain barrier (BBB) endothelium among others. It has been recently suggested that premorbid conditions such as TS may exacerbate post-TBI brain damage and impact recovery. METHODS Our study investigated the mechanisms underlying the exacerbation of TBI injury by TS using a weight drop model. For this purpose, male C57BL/6J mice, age range 6-8 weeks, were chronically exposed to premorbid TS for 3 weeks. Test animals were then subjected to TBI by guided vertical head weight drop using a 30 g metal weight free felling from an 80 cm distance before reaching the target. We analyzed the physical activity and body weight of the mice before TBI and 1 h, 24 h, and 72 h post-injury. Finally, mice were sacrificed to collect blood and brain samples for subsequent biochemical and molecular analysis. Western blotting was applied to assess the expression of Nrf2 (a critical antioxidant transcription factor) as well as tight junction proteins associated with BBB integrity including ZO-1, Occludin, and Claudin-5 from brain tissues homogenates. Levels of NF-kB (a pro-inflammatory transcript factor which antagonizes Nrf2 activity) and pro-inflammatory cytokines IL-6, IL-10, and TNF-α were assessed in blood samples. RESULTS Our data revealed that premorbid TS promoted significantly increased inflammation and loss of BBB integrity in TBI when compared to TS-Free test mice. Additionally, mice chronically exposed to TS before TBI experienced a more significant weight loss, behavioral and motor activity deficiency, and slower post-TBI recovery when compared to TS-free TBI mice. CONCLUSION The effects of premorbid TS appear consequential to the abrogation of physiological antioxidative and anti-inflammatory response to TBI leading to worsening impairments of the BBB, OS damage, and inflammation. These factors are also likely responsible for the retardation of post-traumatic recovery observed in these animals.

中文翻译：

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慢性吸烟对创伤后脑损伤结果和恢复的脑血管和神经系统影响：一项体内研究。


背景技术创伤性脑损伤(TBI)是全世界脑血管和神经损伤的最常见原因之一。为此，烟草烟雾（TS）已被证明可通过针对血脑屏障（BBB）内皮等的氧化应激（OS）刺激，促进血管炎症、神经血管损伤以及脑血管和神经系统疾病的风险。最近有人提出，诸如 TS 之类的病前状况可能会加剧 TBI 后的脑损伤并影响康复。方法 我们的研究使用体重下降模型研究了 TS 加剧 TBI 损伤的机制。为此，将年龄范围为 6-8 周的雄性 C57BL/6J 小鼠长期暴露于病前 TS 3 周。然后，在到达目标之前，使用 30 克金属自由坠落从 80 厘米距离引导测试动物进行 TBI。我们分析了 TBI 前以及受伤后 1 小时、24 小时和 72 小时小鼠的体力活动和体重。最后，处死小鼠以收集血液和脑样本用于随后的生化和分子分析。应用蛋白质印迹法评估 Nrf2（一种关键的抗氧化转录因子）以及与 BBB 完整性相关的紧密连接蛋白（包括脑组织匀浆中的 ZO-1、Occludin 和 Claudin-5）的表达。评估血液样本中 NF-kB（一种拮抗 Nrf2 活性的促炎转录因子）和促炎细胞因子 IL-6、IL-10 和 TNF-α 的水平。结果我们的数据显示，与无 TS 的测试小鼠相比，病前 TS 显着增加了 TBI 中的炎症和 BBB 完整性的丧失。 此外，与未接触 TS 的 TBI 小鼠相比，在 TBI 之前长期暴露于 TS 的小鼠体重减轻更显着，行为和运动活动缺乏，并且 TBI 后恢复更慢。结论 病前 TS 的影响似乎是 TBI 生理抗氧化和抗炎反应消失的结果，导致 BBB 损伤、OS 损伤和炎症恶化。这些因素也可能是在这些动物中观察到的创伤后恢复迟缓的原因。