Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan, Republic of China.
Sci Rep. 2017 Jan 12;7:40111. doi: 10.1038/srep40111.
The onset of hepatic encephalopathy (HE) in liver failure is associated with high mortality; the underlying mechanism is undecided. Here we report that in an acute liver failure model employing intraperitoneal administration of thioacetamide in Sprague-Dawley rats, diffusion weighted imaging revealed a progressive reduction in apparent diffusion coefficient in the brain stem. Diffusion tensor imaging further showed that the connectivity between nucleus tractus solitarii (NTS), the terminal site of baroreceptor afferents in brain stem and rostral ventrolateral medulla (RVLM), the origin of sympathetic innervation of blood vessels, was progressively disrupted until its disappearance, coincidental with the irreversible cessation of baroreflex-mediated sympathetic vasomotor tone signifying clinically the occurrence of brain death. In addition, superoxide, nitric oxide, peroxynitrite and ammonia levels in the NTS or RVLM were elevated, alongside swelling of astroctytes. A scavenger of peroxynitrite, but not an antioxidant, delivered intracisternally reversed all these events. We conclude that nitrosative stress because of augmented peroxynitrite related to accumulation of ammonia and swelling of astrocytes in the NTS or RVLM, leading to cytotoxic edema in the brain stem and severance of the NTS-RVLM connectivity, underpins the defunct baroreflex-mediated sympathetic vasomotor tone that accounts for the high mortality associated with HE.
肝性脑病（HE）在肝衰竭中的发作与高死亡率相关；其潜在机制尚未确定。在这里，我们报告了在采用腹腔内给予硫代乙酰胺的急性肝衰竭模型中，弥散加权成像显示脑干中表观弥散系数逐渐降低。弥散张量成像进一步显示，孤束核（NTS）与延髓头端腹外侧区（RVLM）之间的连接逐渐中断，后者是血管交感神经支配的起源，直至其消失，与不可逆停止的压力感受反射介导的交感血管张力相一致，临床上表示脑死亡的发生。此外，NTS 或 RVLM 中的超氧化物、一氧化氮、过氧亚硝酸盐和氨水平升高，星形胶质细胞肿胀。而 NTS 或 RVLM 内给予过氧亚硝酸盐清除剂而非抗氧化剂可逆转所有这些事件。我们得出结论，由于与氨积累和星形胶质细胞肿胀相关的过氧亚硝酸盐增加导致的硝化应激，导致脑干细胞毒性水肿和 NTS-RVLM 连接中断，这构成了与 HE 相关的高死亡率的无功能压力感受反射介导的交感血管张力的基础。
