The Blood-Brain Barrier in Acute Liver Failure

2015 ◽  
pp. 232-239
Author(s):  
D. F. Schafer
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain

scholarly journals Insight into microRNAs-Mediated Communication between Liver and Brain: A Possible Approach for Understanding Acute Liver Failure?

2021 ◽  
Vol 23 (1) ◽  
pp. 224
Author(s):  
Karolina Orzeł-Gajowik ◽  
Krzysztof Milewski ◽  
Magdalena Zielińska
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Blood Brain Barrier ◽  
Neuropsychiatric Symptoms ◽  
Hepatic Function ◽  
Brain Barrier ◽  
Circulating Mirnas ◽  
Blood Brain ◽  
Micro Rnas ◽  
Functional Components

Acute liver failure (ALF) is a life-threatening consequence of hepatic function rapid loss without preexisting liver disease. ALF may result in a spectrum of neuropsychiatric symptoms that encompasses cognitive impairment, coma, and often death, collectively defined as acute hepatic encephalopathy (HE). Micro RNAs are small non-coding RNAs that modulate gene expression and are extensively verified as biomarker candidates in various diseases. Our systematic literature review based on the last decade’s reports involving a total of 852 ALF patients, determined 205 altered circulating miRNAs, of which 25 miRNAs were altered in the blood, regardless of study design and methodology. Selected 25 miRNAs, emerging predominantly from the analyses of samples obtained from acetaminophen overdosed patients, represent the most promising biomarker candidates for a diagnostic panel for symptomatic ALF. We discussed the role of selected miRNAs in the context of tissue-specific origin and its possible regulatory role for molecular pathways involved in blood–brain barrier function. The defined several common pathways for 15 differently altered miRNAs were relevant to cellular community processes, indicating loss of intercellular, structural, and functional components, which may result in blood-brain barrier impairment and brain dysfunction. However, a causational relationship between circulating miRNAs differential expression, and particular clinical features of ALF, has to be demonstrated in a further study.

scholarly journals Alterations of Blood-Brain Barrier and Associated Factors in Acute Liver Failure

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Wei Cui ◽  
Cui-Ming Sun ◽  
Pei Liu
Keyword(s):  
Tight Junction ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Brain Edema ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Brain Capillary ◽  
Blood Brain ◽  
Capillary Endothelial Cells

Brain edema in acute liver failure (ALF) remains lethal. Cytotoxic mechanisms associated with brain edema have been well recognized, but the role of vasogenic mechanisms of brain edema has not been explored. Intact tight junctions (TJs) between brain capillary endothelial cells are critical for normal BBB function. Recent reports found significant alterations in the tight junction elements including occludin and claudin-5, suggesting a vasogenic injury in the blood-brain barrier (BBB) integrity. However, the role of TJ in ALF has not been completely understood. This paper reviews the role of the paracellular tight junction in the increased selective BBB permeability that leads to brain edema in ALF and furthermore explores the effect of systemic inflammatory cytokines on the tight junction dysfunction.

scholarly journals TIMP-1 Attenuates Blood–Brain Barrier Permeability in Mice with Acute Liver Failure

2013 ◽  
Vol 33 (7) ◽  
pp. 1041-1049 ◽  
Author(s):  
Feng Chen ◽  
Evette S Radisky ◽  
Pritam Das ◽  
Jyotica Batra ◽  
Toshiyuki Hata ◽  
...  
Keyword(s):  
Liver Failure ◽  
Acute Liver Failure ◽  
Blood Brain Barrier ◽  
Growth Factor Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Brain Barrier ◽  
Sodium Fluorescein ◽  
Blood Brain ◽  
Junction Protein ◽  
Bbb Permeability

Blood-brain barrier (BBB) dysfunction in acute liver failure (ALF) results in increased BBB permeability that often precludes the patients from obtaining a life-saving liver transplantation. It remains controversial whether matrix metalloproteinase-9 (MMP-9) from the injured liver contributes to the deregulation of BBB function in ALF. We selectively upregulated a physiologic inhibitor of MMP-9 (TIMP-1) with a single intracerebroventricular injection of TIMP-1 cDNA plasmids at 48 and 72 hours, or with pegylated-TIMP-1 protein. Acute liver failure was induced with tumor necrosis factor-α and D-(+)-galactosamine in mice. Permeability of BBB was assessed with sodium fluorescein (NaF) extravasation. We found a significant increase in TIMP-1 within the central nervous system (CNS) after the administration of TIMP-1 cDNA plasmids and that increased TIMP-1 within the CNS resulted in an attenuation of BBB permeability, a reduction in activation of epidermal growth factor receptor and p38 mitogen-activated protein kinase signals, and a restoration of the tight junction protein occludin in mice with experimental ALF. Pegylated TIMP-1 provided similar protection against BBB permeability in mice with ALF. Our results provided a proof of principle that MMP-9 contributes to the BBB dysfunction in ALF and suggests a potential therapeutic role of TIMP-1 in ALF.

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