Estrogen Alleviates Sex-Dependent Differences in Lung Bacterial Clearance and Mortality Secondary to Bacterial Pneumonia after Traumatic Brain Injury.
Estrogen Alleviates Sex-Dependent Differences in Lung Bacterial Clearance and Mortality Secondary to Bacterial Pneumonia after Traumatic Brain Injury.
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DOI：
10.1089/neu.2020.7327
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发表时间：
2020-11
影响因子：
4.2
通讯作者：
J. Pittet;Parker J Hu;Jaideep Honavar;A. Brandon;Cilina A. Evans;Rebekah Muthalaly;Q. Ding;B. Wagener
中科院分区：
文献类型：
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作者：
J. Pittet;Parker J Hu;Jaideep Honavar;A. Brandon;Cilina A. Evans;Rebekah Muthalaly;Q. Ding;B. Wagener
创伤性脑损伤（TBI）是46岁以下患者与损伤相关的死亡和残疾的主要原因。最初损伤的幸存者经常忍受全身并发症，如肺部感染，铜绿假单胞菌是重症监护病房中医院获得性肺炎的最常见原因之一。女性患者在创伤性脑损伤后发生继发性肺炎的可能性较小，临床前研究表明，创伤后雌激素具有有益的作用。因此，我们假设雌性小鼠在TBI后铜绿假单胞菌肺炎后的死亡率较低。我们采用了一种小鼠TBI模型，随后是铜绿假单胞菌肺炎。与雌性小鼠相比，雄性小鼠在TBI后肺炎后具有更高的死亡率和受损的肺细菌清除率。这被证实是性激素的差异，因为卵巢切除的野生型小鼠的死亡率和肺部细菌清除率与雄性小鼠相似。铜绿假单胞菌感染后，雌雄肺泡巨噬细胞分泌肿瘤坏死因子-α存在差异。最后，给雄性或切除卵巢的野生型雌性小鼠注射雌激素，恢复了肺部细菌清除率，防止了死亡。我们的TBI继发铜绿假单胞菌肺炎模型是第一个揭示继发性长期TBI并发症性别二态性的模型。
Traumatic brain injury (TBI) is the leading cause of injury-related death and disability in patients under the age of 46 years. Survivors of the initial injury often endure systemic complications such as pulmonary infection and Pseudomonas aeruginosa is one of the most common causes of nosocomial pneumonia in intensive care units. Female patients are less likely to develop secondary pneumonia after TBI and preclinical studies have revealed a salutary role for estrogen after trauma. Therefore, we hypothesized that female mice would experience less mortality after post-TBI pneumonia with P. aeruginosa. We employed a mouse model of TBI followed by P. aeruginosa pneumonia. Male mice had greater mortality and impaired lung bacterial clearance after post-TBI pneumonia compared to female mice. This was confirmed as a difference in sex hormones as oophorectomized wild-type mice had mortality and lung bacterial clearance similar to male mice. There were differences in tumor necrosis factor-α secretion in male and female alveolar macrophages after P. aeruginosa infection. Finally, injection of male or oophorectomized wild-type female mice with estrogen restored lung bacterial clearance and prevented mortality. Our model of TBI followed by P. aeruginosa pneumonia is among the first to reveal sex dimorphism in secondary, long-term TBI complications.