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The neurogliovascular unit in hepatic encephalopathy

Wouter Claeys (UGent) , Lien Van Hoecke (UGent) , Sander Lefere (UGent) , Anja Geerts (UGent) , Xavier Verhelst (UGent) , Hans Van Vlierberghe (UGent) , Helena Degroote (UGent) , Lindsey Devisscher (UGent) , Roosmarijn Vandenbroucke (UGent) and Christophe Van Steenkiste
(2021) JHEP REPORTS. 3(5).
Author
Organization
Abstract
Hepatic encephalopathy (HE) is a neurological complication of hepatic dysfunction and portosystemic shunting. It is highly prevalent in patients with cirrhosis and is associated with poor outcomes. New insights into the role of peripheral origins in HE have led to the development of innovative treatment strategies like faecal microbiota transplantation. However, this broadening of view has not been applied fully to perturbations in the central nervous system. The old paradigm that HE is the clinical manifestation of ammonia-induced astrocyte dysfunction and its secondary neuronal consequences requires updating. In this review, we will use the holistic concept of the neurogliovascular unit to describe central nervous system disturbances in HE, an approach that has proven instrumental in other neurological disorders. We will describe HE as a global dysfunction of the neurogliovascular unit, where blood flow and nutrient supply to the brain, as well as the function of the blood-brain barrier, are impaired. This leads to an accumulation of neurotoxic substances, chief among them ammonia and inflammatory mediators, causing dysfunction of astrocytes and microglia. Finally, glymphatic dysfunction impairs the clearance of these neurotoxins, further aggravating their effect on the brain. Taking a broader view of central nervous system alterations in liver disease could serve as the basis for further research into the specific brain pathophysiology of HE, as well as the development of therapeutic strategies specifically aimed at counteracting the often irreversible central nervous system damage seen in these patients. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).
Keywords
NGVU, Ammonia, Systemic inflammation, Cirrhosis, Acute Liver Failure, Energy metabolism, Bloodbrain barrier, Brain edema, Oxidative stress, Neuroinflammation, Glymphatic system, BLOOD-BRAIN-BARRIER, ACUTE LIVER-FAILURE, MAGNETIC-RESONANCE-SPECTROSCOPY, CULTURED RAT ASTROCYTES, BILE-DUCT LIGATION, OXIDATIVE STRESS, ENERGY-METABOLISM, DECOMPENSATED CIRRHOSIS, CEREBRAL-CORTEX, UP-REGULATION

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Citation

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MLA
Claeys, Wouter, et al. “The Neurogliovascular Unit in Hepatic Encephalopathy.” JHEP REPORTS, vol. 3, no. 5, 2021, doi:10.1016/j.jhepr.2021.100352.
APA
Claeys, W., Van Hoecke, L., Lefere, S., Geerts, A., Verhelst, X., Van Vlierberghe, H., … Van Steenkiste, C. (2021). The neurogliovascular unit in hepatic encephalopathy. JHEP REPORTS, 3(5). https://doi.org/10.1016/j.jhepr.2021.100352
Chicago author-date
Claeys, Wouter, Lien Van Hoecke, Sander Lefere, Anja Geerts, Xavier Verhelst, Hans Van Vlierberghe, Helena Degroote, Lindsey Devisscher, Roosmarijn Vandenbroucke, and Christophe Van Steenkiste. 2021. “The Neurogliovascular Unit in Hepatic Encephalopathy.” JHEP REPORTS 3 (5). https://doi.org/10.1016/j.jhepr.2021.100352.
Chicago author-date (all authors)
Claeys, Wouter, Lien Van Hoecke, Sander Lefere, Anja Geerts, Xavier Verhelst, Hans Van Vlierberghe, Helena Degroote, Lindsey Devisscher, Roosmarijn Vandenbroucke, and Christophe Van Steenkiste. 2021. “The Neurogliovascular Unit in Hepatic Encephalopathy.” JHEP REPORTS 3 (5). doi:10.1016/j.jhepr.2021.100352.
Vancouver
1.
Claeys W, Van Hoecke L, Lefere S, Geerts A, Verhelst X, Van Vlierberghe H, et al. The neurogliovascular unit in hepatic encephalopathy. JHEP REPORTS. 2021;3(5).
IEEE
[1]
W. Claeys et al., “The neurogliovascular unit in hepatic encephalopathy,” JHEP REPORTS, vol. 3, no. 5, 2021.
@article{8725158,
  abstract     = {{Hepatic encephalopathy (HE) is a neurological complication of hepatic dysfunction and portosystemic shunting. It is highly prevalent in patients with cirrhosis and is associated with poor outcomes. New insights into the role of peripheral origins in HE have led to the development of innovative treatment strategies like faecal microbiota transplantation. However, this broadening of view has not been applied fully to perturbations in the central nervous system. The old paradigm that HE is the clinical manifestation of ammonia-induced astrocyte dysfunction and its secondary neuronal consequences requires updating. In this review, we will use the holistic concept of the neurogliovascular unit to describe central nervous system disturbances in HE, an approach that has proven instrumental in other neurological disorders. We will describe HE as a global dysfunction of the neurogliovascular unit, where blood flow and nutrient supply to the brain, as well as the function of the blood-brain barrier, are impaired. This leads to an accumulation of neurotoxic substances, chief among them ammonia and inflammatory mediators, causing dysfunction of astrocytes and microglia. Finally, glymphatic dysfunction impairs the clearance of these neurotoxins, further aggravating their effect on the brain. Taking a broader view of central nervous system alterations in liver disease could serve as the basis for further research into the specific brain pathophysiology of HE, as well as the development of therapeutic strategies specifically aimed at counteracting the often irreversible central nervous system damage seen in these patients. (C) 2021 The Authors. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver (EASL).}},
  articleno    = {{100352}},
  author       = {{Claeys, Wouter and Van Hoecke, Lien and Lefere, Sander and Geerts, Anja and Verhelst, Xavier and Van Vlierberghe, Hans and Degroote, Helena and Devisscher, Lindsey and Vandenbroucke, Roosmarijn and Van Steenkiste, Christophe}},
  issn         = {{2589-5559}},
  journal      = {{JHEP REPORTS}},
  keywords     = {{NGVU,Ammonia,Systemic inflammation,Cirrhosis,Acute Liver Failure,Energy metabolism,Bloodbrain barrier,Brain edema,Oxidative stress,Neuroinflammation,Glymphatic system,BLOOD-BRAIN-BARRIER,ACUTE LIVER-FAILURE,MAGNETIC-RESONANCE-SPECTROSCOPY,CULTURED RAT ASTROCYTES,BILE-DUCT LIGATION,OXIDATIVE STRESS,ENERGY-METABOLISM,DECOMPENSATED CIRRHOSIS,CEREBRAL-CORTEX,UP-REGULATION}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{15}},
  title        = {{The neurogliovascular unit in hepatic encephalopathy}},
  url          = {{http://doi.org/10.1016/j.jhepr.2021.100352}},
  volume       = {{3}},
  year         = {{2021}},
}
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