PDF(Pubmed)
Abstract：
Pneumonia is a common comorbidity in patients with severe traumatic brain injury (TBI), and is associated with increased morbidity and mortality. In this study, we established a model of intratracheal Klebsiella pneumoniae administration in young adult male and female mice, at 4 days following an experimental TBI, to investigate how K. pneumoniae infection influences acute post-TBI outcomes. A dose-response curve determined the optimal dose of K. pneumoniae for inoculation (1 x 10^6 colony forming units), and administration at 4 days post-TBI resulted in transient body weight loss and sickness behaviors (hypoactivity and acute dyspnea). K. pneumoniae infection led to an increase in pro-inflammatory cytokines in serum and bronchoalveolar lavage fluid at 24 h post-infection, in both TBI and sham (uninjured) mice. By 7 days, when myeloperoxidase + neutrophil numbers had returned to baseline in all groups, lung histopathology was observed with an increase in airspace size in TBI + K. pneumoniae mice compared to TBI + vehicle mice. In the brain, increased neuroinflammatory gene expression was observed acutely in response to TBI, with an exacerbated increase in Ccl2 and Hmox1 in TBI + K. pneumoniae mice compared to either TBI or K. pneumoniae alone. However, the presence of neuroinflammatory immune cells in the injured brain, and the extent of damage to cortical and hippocampal brain tissue, was comparable between K. pneumoniae and vehicle-treated mice by 7 days. Examination of the fecal microbiome across a time course did not reveal any pronounced effects of either injury or K. pneumoniae on bacterial diversity or abundance. Together, these findings demonstrate that K. pneumoniae lung infection after TBI induces an acute and transient inflammatory response, primarily localized to the lungs with some systemic effects. However, this infection had minimal impact on secondary injury processes in the brain following TBI. Future studies are needed to evaluate the potential longer-term consequences of this dual-hit insult.
摘要：
肺炎是严重创伤性脑损伤（TBI）患者常见的合并症，并与发病率和死亡率增加有关。在这项研究中,我们建立了年轻成年雄性和雌性小鼠气管内肺炎克雷伯菌给药模型，在实验性TBI后4天，研究肺炎克雷伯菌感染如何影响急性TBI后结局。剂量反应曲线确定了肺炎克雷伯菌接种的最佳剂量（1×10^6个菌落形成单位），TBI后4天的给药导致短暂的体重减轻和疾病行为（活动不足和急性呼吸困难）。肺炎克雷伯菌感染导致感染后24小时血清和支气管肺泡灌洗液中的促炎细胞因子增加，在TBI和假（未受伤）小鼠中。7天,当所有组的髓过氧化物酶+中性粒细胞数量恢复到基线时，与TBI+载体小鼠相比,在TBI+肺炎克雷伯氏菌小鼠中观察到肺组织病理学,空域大小增加。在大脑中,在对TBI的反应中急性观察到神经炎症基因表达增加，与单独的TBI或肺炎克雷伯菌相比，TBI+肺炎克雷伯菌小鼠的Ccl2和Hmox1增加加剧。然而,受损大脑中存在神经炎症免疫细胞，以及皮质和海马脑组织的损伤程度，肺炎克雷伯菌和媒介物处理的小鼠在7天之间具有可比性。在一个时间过程中对粪便微生物组的检查未发现损伤或肺炎克雷伯菌对细菌多样性或丰度的任何明显影响。一起,这些研究结果表明，肺炎克雷伯菌肺部感染后可诱导急性和短暂的炎症反应，主要局限在肺部，有一些全身效应。然而,这种感染对TBI后大脑的继发性损伤过程影响最小.需要未来的研究来评估这种双重攻击的潜在长期后果。
