Orihuela Carlos J, Fillon Sophie, Smith-Sielicki S Hope, El Kasmi Karim C, Gao Geli, Soulis Konstantinos, Patil Avinash, Murray Peter J, Tuomanen Elaine I
Infectious Diseases, St. Jude Children's Research Hospital, Mailstop 320 IRC 8057, 332 N. Lauderdale Rd., Memphis, TN 38105, USA.
Infect Immun. 2006 Jul;74(7):3783-9. doi: 10.1128/IAI.00022-06.
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.
在无脑膜炎的脓毒症病程中可发生神经元功能障碍。在实验性肺炎球菌菌血症数小时内，海马体中观察到脓毒症相关神经元损伤（SAND）。用纯化的细菌细胞壁进行血管内攻击可重现SAND。SAND在血小板活化因子受体（PAFr）基因敲除小鼠中持续存在，但在缺乏细胞壁识别蛋白Toll样受体2（TLR2）和核苷酸结合寡聚化结构域蛋白2（Nod2）的小鼠以及巨噬细胞中白细胞介素-10（IL-10）过表达的小鼠中部分减轻。因此，细胞壁通过IL-10可抑制的炎症事件驱动SAND。用胞二磷胆碱治疗可改善SAND，这表明它可能是一种有效的辅助治疗方法，可提高脓毒症患者的生存率并减少器官损伤。
