Brain edema in acute liver failure: mechanisms and concepts

Kakulavarapu V. Rama Rao, Arumugam R. Jayakumar, Michael D Norenberg

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Brain edema and associated increase in intracranial pressure continue to be lethal complications of acute liver failure (ALF). Abundant evidence suggests that the edema in ALF is largely cytotoxic brought about by swelling of astrocytes. Elevated blood and brain ammonia levels have been strongly implicated in the development of the brain edema. Additionally, inflammation and sepsis have been shown to contribute to the astrocyte swelling/brain edema in the setting of ALF. We posit that ammonia initiates a number of signaling events, including oxidative/nitrative stress (ONS), the mitochondrial permeability transition (mPT), activation of the transcription factor (NF-κB) and signaling kinases, all of which have been shown to contribute to the mechanism of astrocyte swelling. All of these factors also impact ion-transporters, including Na+, K+, Cl cotransporter and the sulfonylurea receptor 1, as well as the water channel protein aquaporin-4 resulting in a perturbation of cellular ion and water homeostasis, ultimately resulting in astrocyte swelling/brain edema. All of these events are also potentiated by inflammation. This article reviews contemporary knowledge regarding mechanisms of astrocyte swelling/brain edema formation which hopefully will facilitate the identification of therapeutic targets capable of mitigating the brain edema associated with ALF.

Original languageEnglish
Pages (from-to)927-936
Number of pages10
JournalMetabolic Brain Disease
Volume29
Issue number4
DOIs
StatePublished - Jan 1 2014

Fingerprint

Acute Liver Failure
Brain Edema
Liver
Brain
Astrocytes
Swelling
Ammonia
Sodium-Potassium-Chloride Symporters
Sulfonylurea Receptors
Aquaporin 4
Ions
Inflammation
Aquaporins
Intracranial Hypertension
Oxidative stress
Permeability
Edema
Sepsis
Oxidative Stress
Homeostasis

Keywords

  • Acute liver failure
  • Ammonia
  • Aquaporin-4
  • Astrocytes
  • Brain edema
  • Endothelial cells
  • Hepatic encephalopathy
  • Inflammation
  • Ion transporters
  • Microglia
  • Oxidative/nitrative stress
  • Vasogenic edema

ASJC Scopus subject areas

  • Clinical Neurology
  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Brain edema in acute liver failure : mechanisms and concepts. / Rama Rao, Kakulavarapu V.; Jayakumar, Arumugam R.; Norenberg, Michael D.

In: Metabolic Brain Disease, Vol. 29, No. 4, 01.01.2014, p. 927-936.

Research output: Contribution to journalArticle

Rama Rao, Kakulavarapu V. ; Jayakumar, Arumugam R. ; Norenberg, Michael D. / Brain edema in acute liver failure : mechanisms and concepts. In: Metabolic Brain Disease. 2014 ; Vol. 29, No. 4. pp. 927-936.
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