The neurogliovascular unit in hepatic encephalopathy
| Autor: | Christophe Van Steenkiste, Lindsey Devisscher, Sander Lefere, Wouter Claeys, Xavier Verhelst, Helena Degroote, Anja Geerts, Hans Van Vlierberghe, Roosmarijn E. Vandenbroucke, Lien Van Hoecke |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Cirrhosis
BCRP breast cancer resistance protein ENERGY-METABOLISM mPT mitochondrial pore transition Review HO-1 heme oxygenase 1 UP-REGULATION SUR1 sulfonylurea receptor 1 CSF cerebrospinal fluid TNF tumour necrosis factor GS glutamine synthetase AOM azoxymethane Neuroinflammation ZO zonula occludens CULTURED RAT ASTROCYTES P-gp P-glycoprotein Medicine and Health Sciences Immunology and Allergy Medicine TGFβ transforming growth factor beta Hepatic encephalopathy Blood-brain barrier CE cerebral oedema Microglia CCL chemokine ligand ABC ATP-binding cassette Gastroenterology MAGNETIC-RESONANCE-SPECTROSCOPY CLDN claudin OCLN occludin IL- interleukin TJ tight junction medicine.anatomical_structure Aquaporin 4 NGVU ACUTE LIVER-FAILURE Glymphatic system BBB blood-brain barrier Central nervous system Acute Liver Failure AQP4 aquaporin 4 ONS oxidative and nitrosative stress BDL bile duct ligation CNS central nervous system Blood–brain barrier S1PR2 sphingosine-1-phosphate receptor 2 Ammonia ALF acute liver failure CEREBRAL-CORTEX CCR C-C chemokine receptor Internal Medicine NKCC1 Na-K-2Cl cotransporter 1 TNFR1 tumour necrosis factor receptor 1 MMP-9 matrix metalloproteinase 9 PSS portosystemic shunt BILE-DUCT LIGATION TAA thioacetamide Systemic inflammation Hepatology BLOOD-BRAIN-BARRIER business.industry Energy metabolism medicine.disease AD acute decompensation HE hepatic encephalopathy PCA portacaval anastomosis MRP multidrug resistance associated protein Oxidative stress ACLF acute-on-chronic liver failure Brain edema CLD chronic liver disease Human medicine NGVU neurogliovascular unit DECOMPENSATED CIRRHOSIS business Neuroscience Bloodbrain barrier |
| Zdroj: | JHEP Reports JHEP REPORTS |
| ISSN: | 2589-5559 |
| DOI: | 10.1016/j.jhepr.2021.100352 |
| Popis: | 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). |
| Databáze: | OpenAIRE |
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