Miyao Mariko, Hirotsu Akiko, Tatsumi Kenichiro, Tanaka Tomoharu
Department of Anesthesia, Kyoto University Hospital, 54 Kawahara-Cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Department of Anesthesia, Hyogo Prefectural Amagasaki General Medical Center, 2-17-77 Higashi Naniwacho, Amagasaki, Hyogo 660-8550, Japan.
Heliyon. 2023 Jun 2;9(6):e16904. doi: 10.1016/j.heliyon.2023.e16904. eCollection 2023 Jun.
Neuroinflammation can occur during sepsis and is now regarded as the main mechanism underlying various related central nervous system (CNS) disorders. Another well-known factor causing neuroinflammation is psychological stress. In the current study, we examined the effects of prior exposure to stress on sepsis-induced neuroinflammation and CNS symptoms.
Balb/c mice were subjected to wet bedding stress for 2 days, then lipopolysaccharide (LPS) was intraperitoneally administered. For examining the neuroinflammation, the expression of proinflammatory cytokines and NF-κB activity in the brain was analyzed by RT-PCR and ELISA-based assay. Additionally, immunohistochemical study using Iba-1 was performed. Finally, behavior tests were examined one month after LPS treatment.
Stress exposure induced the upregulation of IL-1β, IL-6 and TNFα mRNA in the cerebral cortex 4 h after LPS administration. Suggesting an underlying mechanism, LPS-induced NF-κB activation was significantly upregulated with stress in the brain. Histologically, microglia in the cerebral cortex were reactive and became more abundant with stress, while these effects were further increased with LPS injection. Behavioral analysis conducted showed a significant increase of anxiety-like behaviors in the stressed mice. These results suggest that prior exposure to stress exacerbates neuroinflammation during sepsis and induces long-term behavior changes.
神经炎症可在脓毒症期间发生，目前被认为是各种相关中枢神经系统（CNS）疾病的主要潜在机制。另一个导致神经炎症的众所周知的因素是心理压力。在本研究中，我们研究了先前暴露于压力对脓毒症诱导的神经炎症和中枢神经系统症状的影响。
将Balb/c小鼠置于湿垫料应激环境中2天，然后腹腔注射脂多糖（LPS）。为了检测神经炎症，通过逆转录聚合酶链反应（RT-PCR）和基于酶联免疫吸附测定（ELISA）的方法分析大脑中促炎细胞因子的表达和核因子κB（NF-κB）的活性。此外，使用离子钙结合衔接分子1（Iba-1）进行免疫组织化学研究。最后，在LPS治疗一个月后进行行为测试。
应激暴露导致LPS给药后4小时大脑皮质中白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子α（TNFα）mRNA上调。作为一种潜在机制，LPS诱导的NF-κB激活在大脑中因应激而显著上调。组织学上，大脑皮质中的小胶质细胞具有反应性，并且随着应激而变得更加丰富，而这些效应在注射LPS后进一步增强。进行的行为分析显示，应激小鼠的焦虑样行为显著增加。这些结果表明，先前暴露于压力会加剧脓毒症期间的神经炎症并诱导长期行为改变。
