The neurogliovascular unit in hepatic encephalopathy.
ABC, ATP-binding cassette
ACLF, acute-on-chronic liver failure
AD, acute decompensation
ALF, acute liver failure
AOM, azoxymethane
AQP4, aquaporin 4
Acute Liver Failure
Ammonia
BBB, blood-brain barrier
BCRP, breast cancer resistance protein
BDL, bile duct ligation
Blood-brain barrier
Brain edema
CCL, chemokine ligand
CCR, C-C chemokine receptor
CE, cerebral oedema
CLD, chronic liver disease
CLDN, claudin
CNS, central nervous system
CSF, cerebrospinal fluid
Cirrhosis
Energy metabolism
GS, glutamine synthetase
Glymphatic system
HE, hepatic encephalopathy
HO-1, heme oxygenase 1
IL-, interleukin
MMP-9, matrix metalloproteinase 9
MRP, multidrug resistance associated protein
NGVU
NGVU, neurogliovascular unit
NKCC1, Na-K-2Cl cotransporter 1
Neuroinflammation
OCLN, occludin
ONS, oxidative and nitrosative stress
Oxidative stress
P-gp, P-glycoprotein
PCA, portacaval anastomosis
PSS, portosystemic shunt
S1PR2, sphingosine-1-phosphate receptor 2
SUR1, sulfonylurea receptor 1
Systemic inflammation
TAA, thioacetamide
TGFβ, transforming growth factor beta
TJ, tight junction
TNF, tumour necrosis factor
TNFR1, tumour necrosis factor receptor 1
ZO, zonula occludens
mPT, mitochondrial pore transition
Journal
JHEP reports : innovation in hepatology
ISSN: 2589-5559
Titre abrégé: JHEP Rep
Pays: Netherlands
ID NLM: 101761237
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
received:
30
04
2021
revised:
14
07
2021
accepted:
23
07
2021
entrez:
6
10
2021
pubmed:
7
10
2021
medline:
7
10
2021
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 34611619
doi: 10.1016/j.jhepr.2021.100352
pii: S2589-5559(21)00128-2
pmc: PMC8476774
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
100352Informations de copyright
© 2021 The Authors.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.
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