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Metabolic Brain Disease

, Volume 28, Issue 2, pp 145–150 | Cite as

Liver-brain proinflammatory signalling in acute liver failure: Role in the pathogenesis of hepatic encephalopathy and brain edema

  • Chantal Bémeur
  • Roger F. ButterworthEmail author
Original Paper

Abstract

A robust neuroinflammatory response characterized by microglial activation and increased brain production of pro-inflammatory cytokines is common in acute liver failure (ALF). Mechanisms proposed to explain the neuroinflammatory response in ALF include direct effects of systemically-derived proinflammatory cytokines and the effects of brain lactate accumulation on pro-inflammatory cytokine release from activated microglia. Cell culture studies reveal a positive synergistic effect of ammonia and pro-inflammatory cytokines on the expression of proteins involved in glutamate homeostasis and in oxidative/nitrosative stress. Proinflammatory cytokines have the capacity to alter blood–brain barrier (BBB) integrity and preliminary studies suggest that the presence of infection in ALF results in rupture of the BBB and vasogenic brain edema. Treatments currently under investigation that are effective in prevention of encephalopathy and brain edema in ALF which are aimed at reduction of neuroinflammation in ALF include mild hypothermia, albumin dialysis systems, N-acetyl cysteine and the antibiotic minocycline with potent anti-inflammatory actions that are distinct from its anti-microbial properties.

Keywords

Hepatic encephalopathy Neuroinflammation Cytokines Microglia Blood–brain barrier Hypothermia Ammonia 

Notes

Acknowledgements

Studies from the author’s research unit were funded by operating grants from The Canadian Institutes of Health Research (CIHR).

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Copyright information

© Springer Science+Business Media New York 2012

Authors and Affiliations

  1. 1.Département de nutrition, Faculté de médecineUniversité de MontréalMontréalCanada
  2. 2.Unité de recherche en neurosciences, Hôpital Saint-Luc (CHUM)Université de MontréalMontréalCanada
  3. 3.Neuroscience Research UnitHôpital Saint-Luc (CHUM)MontrealCanada

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