New concepts in the mechanism of ammonia-induced astrocyte swelling

Michael D Norenberg, A. R. Jayakumar, K. V. Rama Rao, K. S. Panickar

Research output: Contribution to journalArticle

126 Citations (Scopus)

Abstract

It is generally accepted that astrocyte swelling forms the major anatomic substrate of the edema associated with acute liver failure (ALF) and that ammonia represents a major etiological factor in its causation. The mechanisms leading to such swelling, however, remain elusive. Recent studies have invoked the role of oxidative stress in the mechanism of hepatic encephalopathy (HE), as well as in the brain edema related to ALF. This article summarizes the evidence for oxidative stress as a major pathogenetic factor in HE/ALF and discusses mechanisms that are triggered by oxidative stress, including the induction of the mitochondrial permeability transition (MPT) and activation of signaling kinases. We propose that a cascade of events initiated by ammonia-induced oxidative stress results in cell volume dysregulation leading to cell swelling/brain edema. Blockade of this cascade may provide novel therapies for the brain edema associated with ALF.

Original languageEnglish
Pages (from-to)219-234
Number of pages16
JournalMetabolic Brain Disease
Volume22
Issue number3-4
DOIs
StatePublished - Dec 1 2007

Fingerprint

Oxidative stress
Acute Liver Failure
Ammonia
Astrocytes
Liver
Swelling
Brain Edema
Oxidative Stress
Brain
Hepatic Encephalopathy
Cell Size
Causality
Permeability
Edema
Phosphotransferases
Chemical activation
Substrates
Therapeutics

Keywords

  • Acute liver failure
  • Ammonia
  • Astrocytes
  • Brain edema
  • Cell swelling
  • Glutamine
  • Hepatic encephalopathy
  • Mitochondrial permeability transition
  • Nitrosative stress
  • Oxidative stress
  • Signaling kinases

ASJC Scopus subject areas

  • Clinical Neurology
  • Biochemistry
  • Neuroscience(all)

Cite this

New concepts in the mechanism of ammonia-induced astrocyte swelling. / Norenberg, Michael D; Jayakumar, A. R.; Rama Rao, K. V.; Panickar, K. S.

In: Metabolic Brain Disease, Vol. 22, No. 3-4, 01.12.2007, p. 219-234.

Research output: Contribution to journalArticle

Norenberg, Michael D ; Jayakumar, A. R. ; Rama Rao, K. V. ; Panickar, K. S. / New concepts in the mechanism of ammonia-induced astrocyte swelling. In: Metabolic Brain Disease. 2007 ; Vol. 22, No. 3-4. pp. 219-234.
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