Fujinami Yoshihisa, Inoue Shigeaki, Ono Yuko, Miyazaki Yusuke, Fujioka Kazumichi, Yamashita Kimihiro, Kotani Joji
Department of Disaster and Emergency and Critical Care Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Department of Surgery, Division of Gastrointestinal Surgery, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
J Clin Med. 2021 Apr 9;10(8):1593. doi: 10.3390/jcm10081593.
Post-intensive care syndrome (PICS) is a physical, cognitive, and mental impairment observed in intensive care unit (ICU) survivors. Although this is an emerging problem in the ICU, how sepsis induces the characteristic symptoms of PICS remains unclear. To develop a model of PICS, we induced sepsis in male C57/B6 mice via sublethal cecum slurry injection and subsequently treated them using ICU-like interventions. At 1-2 weeks post-sepsis induction, we simultaneously evaluated the abilities of the surviving mice using the following behavioral tests: (1) a grip strength test (GST) and a treadmill test for physical assessment, (2) a novel object recognition test (NORT) for cognitive assessment, and (3) an open field test (OFT) and a marble burying test (MBT) for mental assessment. The surviving mice showed a range of deficits, including muscle weakness with significantly decreased grip strength in the GST; decreased total mileage during the treadmill test; anxiety and decreased activity, with significantly decreased time in the central area, and increased duration of immobility in the OFT; and an increased number of buried marbles in the MBT. Given these physical and mental impairments in the surviving mice, our model has the potential to elucidate mechanistic insights and to discover therapeutic targets and new interventions for PICS.
重症监护后综合征(PICS)是在重症监护病房(ICU)幸存者中观察到的一种身体、认知和精神障碍。尽管这在ICU中是一个新出现的问题,但脓毒症如何诱发PICS的特征性症状仍不清楚。为了建立PICS模型,我们通过亚致死剂量的盲肠匀浆注射在雄性C57/B6小鼠中诱发脓毒症,随后使用类似ICU的干预措施对它们进行治疗。在脓毒症诱导后1至2周,我们使用以下行为测试同时评估存活小鼠的能力:(1)握力测试(GST)和跑步机测试用于身体评估,(2)新奇物体识别测试(NORT)用于认知评估,以及(3)旷场试验(OFT)和埋珠试验(MBT)用于精神评估。存活小鼠表现出一系列缺陷,包括在GST中握力显著下降的肌肉无力;跑步机测试期间总里程减少;焦虑和活动减少,在OFT中中央区域的时间显著减少,不动时间增加;以及在MBT中埋珠数量增加。鉴于存活小鼠存在这些身体和精神障碍,我们的模型有潜力阐明机制见解,并发现PICS的治疗靶点和新的干预措施。