Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Instituto de Fisiología y Biofísica "Houssay" (IFIBIO), Laboratorio de Neurofisiopatología, Facultad de Medicina, Argentina.
Curr Neuropharmacol. 2021;19(1):24-44. doi: 10.2174/1570159X18666200220143001.
Infection with Shiga toxin-producing Escherichia coli (STEC) may cause hemorrhagic colitis, hemolytic uremic syndrome (HUS) and encephalopathy. The mortality rate derived from HUS adds up to 5% of the cases, and up to 40% when the central nervous system (CNS) is involved. In addition to the well-known deleterious effect of Stx, the gram-negative STEC releases lipopolysaccharides (LPS) and may induce a variety of inflammatory responses when released in the gut. Common clinical signs of severe CNS injury include sensorimotor, cognitive, emotional and/or autonomic alterations. In the last few years, a number of drugs have been experimentally employed to establish the pathogenesis of, prevent or treat CNS injury by STEC. The strategies in these approaches focus on: 1) inhibition of Stx production and release by STEC, 2) inhibition of Stx bloodstream transport, 3) inhibition of Stx entry into the CNS parenchyma, 4) blockade of deleterious Stx action in neural cells, and 5) inhibition of immune system activation and CNS inflammation. Fast diagnosis of STEC infection, as well as the establishment of early CNS biomarkers of damage, may be determinants of adequate neuropharmacological treatment in time.
产志贺毒素大肠杆菌（STEC）感染可能导致出血性结肠炎、溶血性尿毒症综合征（HUS）和脑病。HUS 导致的死亡率高达 5%，当涉及中枢神经系统（CNS）时，死亡率高达 40%。除了 Stx 众所周知的有害作用外，革兰氏阴性 STEC 还会释放脂多糖（LPS），当在肠道中释放时，可能会引起各种炎症反应。严重 CNS 损伤的常见临床体征包括感觉运动、认知、情绪和/或自主改变。在过去的几年中，已经有许多药物被用于实验，以确定 STEC 引起的 CNS 损伤的发病机制、预防或治疗。这些方法中的策略侧重于：1）抑制 STEC 产生和释放 Stx，2）抑制 Stx 血流运输，3）抑制 Stx 进入 CNS 实质，4）阻断有害 Stx 在神经细胞中的作用，以及 5）抑制免疫系统激活和 CNS 炎症。快速诊断 STEC 感染以及建立早期 CNS 损伤生物标志物，可能是及时进行适当神经药理学治疗的决定因素。
