中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2025, Vol. 20 ›› Issue (12): 3461-3475.doi: 10.4103/NRR.NRR-D-24-00600

• 综述:脑损伤修复保护与再生 • 上一篇    下一篇

星形胶质细胞和小胶质细胞在晚期慢性肝病相关的肝性脑病中的作用：动物研究的经验教训

  

  • 出版日期:2025-12-15 发布日期:2025-03-13

Role of astrocytes and microglia in hepatic encephalopathy associated with advanced chronic liver disease: lessons from animal studies

Wouter Claeys1, 2, 3, 4, Anja Geerts1, 2, 5, Lien Van Hoecke3, 4, Christophe Van Steenkiste6, 7, #, Roosmarijn E. Vandenbroucke3, 4, *, #   

  1. 1 Department of Internal Medicine and Paediatrics, Hepatology Research Unit, Ghent University, Ghent, Belgium;  2 Liver Research Center Ghent, Ghent University, Ghent University Hospital, Ghent, Belgium;  3 Barriers in Inflammation, VIB-UGent Center for Inflammation Research, VIB, Ghent, Belgium;  4 Department of Biomedical Molecular Biology, Ghent University, Ghent, Belgium;  5 Department of Gastroenterology and Hepatology, Ghent University Hospital, Ghent, Belgium;  6 Department of Gastroenterology and Hepatology, Antwerp University, Antwerp, Belgium;  7 Department of Gastroenterology and Hepatology, Maria Middelares Hospital, Ghent, Belgium
  • Online:2025-12-15 Published:2025-03-13
  • Contact: Roosmarijn E. Vandenbroucke, PhD, Roosmarijn.Vandenbroucke@irc.VIB-UGent.be.
  • Supported by:
    This work was supported by grants from the Research Foundation – Flanders (11A6420N, 1268823N to WC and LVH), a FWO Junior Research Project Grant (G055121N to REV), and VIB. AG is a senior clinical researcher of the Research Foundation – Flanders (1805718N).

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摘要： https://orcid.org/0000-0002-8327-620X (Roosmarijn E. Vandenbroucke) 

Abstract: Hepatic encephalopathy, defined as neuropsychiatric dysfunction secondary to liver disease, is a frequent decompensating event in cirrhosis. Its clinical impact is highlighted by a notable increase in patient mortality rates and a concomitant reduction in overall quality of life. Systemically, liver disease, liver function failure, portosystemic shunting, and associated multi-organ dysfunction result in the increase of disease-causing neurotoxins in the circulation, which impairs cerebral homeostasis. Key circulating neurotoxins are ammonia and inflammatory mediators. In the brain, pathophysiology is less well understood, but is thought to be driven by glial cell dysfunction. Astrocytes are the only brain resident cells that have ammonia-metabolizing machinery and are therefore putatively most susceptible to ammonia elevation. Based on a large body of mostly in vitro evidence, ammonia-induced cellular and molecular disturbances include astrocyte swelling and oxidative stress. Microglia, the brain resident macrophages, have been linked to the translation of systemic inflammation to the brain microenvironment. Recent evidence from animal studies has provided novel insights into old and new downstream effects of astrocyte and microglial dysfunction such as toxin clearance disruption and myeloid cell attraction to the central nervous system parenchyma. Furthermore, state of the art research increasingly implicates neuronal dysfunction and possibly even irreversible neuronal cell death. Cell-type specific investigation in animal models highlights the need for critical revision of the contribution of astrocytes and microglia to wellestablished and novel cellular and molecular alterations in hepatic encephalopathy. In this review, we therefore give a current and comprehensive overview of causes, features, and consequences of astrocyte and microglial dysfunction in hepatic encephalopathy, including areas of interest for future investigation.

Key words: ammonia, astrocytes, cirrhosis, hepatic encephalopathy, microglia, neuroinflammation, osmotic stress, oxidative stress, systemic inflammation