Cell wall-mediated neuronal damage in early sepsis
Cell wall-mediated neuronal damage in early sepsis
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DOI：
10.1128/iai.00022-06
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发表时间：
2006-07-01
影响因子：
3.1
通讯作者：
Tuomanen, Elaine I.
中科院分区：
文献类型：
--
作者：
Orihuela, Carlos J.;Fillon, Sophie;Tuomanen, Elaine I.
神经元功能障碍可发生在败血症过程中没有脑膜炎。脓毒症相关的神经元损伤（SAND）在实验性肺炎球菌菌血症的几个小时内观察到海马。用纯化细菌细胞壁进行血管内激发重现SAND。SAND在PAFr（-/-）小鼠中持续存在，但在缺乏细胞壁识别蛋白TLR 2和Nod 2的小鼠以及在巨噬细胞中过表达白细胞介素-10（IL-10）的小鼠中部分减轻。因此，细胞壁通过IL-10抑制的炎症事件驱动SAND。CDP-胆碱治疗可改善SAND，提示其可能是提高脓毒症患者生存率和减少器官损害的有效治疗方法。
Neuronal dysfunction can occur in the course of sepsis without meningitis. Sepsis-associated neuronal damage (SAND) was observed in the hippocampus within hours in experimental pneumococcal bacteremia. Intravascular challenge with purified bacterial cell wall recapitulated SAND. SAND persisted in PAFr(-/-) mice but was partially mitigated in mice lacking cell wall recognition proteins TLR2 and Nod2 and in mice overexpressing interleukin-10 (IL-10) in macrophages. Thus, cell wall drives SAND through IL-10-repressible inflammatory events. Treatment with CDP-choline ameliorated SAND, suggesting that it may be an effective adjunctive therapy to increase survival and reduce organ damage in sepsis.