Xu Su, Zhu Wenjun, Wan Yamin, Wang JiaBei, Chen Xi, Pi Liya, Lobo Mary Kay, Ren Bin, Ying Zhekang, Morris Michael, Cao Qi
1 Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
2 The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
Mol Imaging. 2018 Jan-Dec;17:1536012117749051. doi: 10.1177/1536012117749051.
Minimal hepatic encephalopathy (MHE) is highly prevalent, observed in up to 80% of patients with liver dysfunction. Minimal hepatic encephalopathy is defined as hepatic encephalopathy with cognitive deficits and no grossly evident neurologic abnormalities. Clinical management may be delayed due to the lack of in vivo quantitative methods needed to reveal changes in brain neurobiochemical biomarkers. To gain insight into the development of alcoholic liver disease-induced neurological dysfunction (NDF), a mouse model of late-stage alcoholic liver fibrosis (LALF) was used to investigate changes in neurochemical levels in the thalamus and hippocampus that relate to behavioral changes. Proton magnetic resonance spectroscopy of the brain and behavioral testing were performed to determine neurochemical alterations and their relationships to behavioral changes in LALF. Glutamine levels were higher in both the thalamus and hippocampus of alcohol-treated mice than in controls. Thalamic levels of taurine and creatine were significantly diminished and strongly correlated with alcohol-induced behavioral changes. Chronic long-term alcohol consumption gives rise to advanced liver fibrosis, neurochemical changes in the nuclei, and behavioral changes which may be linked to NDF. Magnetic resonance spectroscopy represents a sensitive and noninvasive measurement of pathological alterations in the brain, which may provide insight into the pathogenesis underlying the development of MHE.
轻微肝性脑病(MHE)极为常见,在高达80%的肝功能不全患者中都有发现。轻微肝性脑病被定义为伴有认知缺陷且无明显神经学异常的肝性脑病。由于缺乏揭示脑神经营生化生物标志物变化所需的体内定量方法,临床管理可能会延迟。为深入了解酒精性肝病所致神经功能障碍(NDF)的发展过程,采用晚期酒精性肝纤维化(LALF)小鼠模型来研究丘脑和海马体中与行为变化相关的神经化学水平变化。对大脑进行质子磁共振波谱分析和行为测试,以确定LALF中的神经化学改变及其与行为变化的关系。酒精处理小鼠的丘脑和海马体中的谷氨酰胺水平均高于对照组。丘脑的牛磺酸和肌酸水平显著降低,且与酒精诱导的行为变化密切相关。长期慢性饮酒会导致晚期肝纤维化、神经核团的神经化学变化以及可能与NDF相关的行为变化。磁共振波谱分析是对大脑病理改变的一种敏感且无创的测量方法,这可能有助于深入了解MHE发生发展的潜在发病机制。