A neurotoxic alcohol exposure paradigm does not induce hepatic encephalopathy

Joel G. Hashimoto, Kristine Wiren, Clare Wilhelm

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Alcohol abuse is associated with neurological dysfunction, brain morphological deficits and frank neurotoxicity. Although these disruptions may be a secondary effect due to hepatic encephalopathy, no clear evidence of causality is available. This study examined whether a 72 h period of alcohol intoxication known to induce physical dependence, followed by a single withdrawal, was sufficient to induce signs of hepatic encephalopathy in male and female mice. Animals were continuously intoxicated via alcohol vapor inhalation, a procedure previously shown to induce significant neurotoxicity in female mice. At peak synchronized withdrawal (8 h following the end of alcohol exposure), blood samples were taken and levels of several liver-regulated markers and brain swelling were characterized. Glutathione levels were also determined in the medial frontal cortex (mFC) and hippocampus. Results revealed elevated levels of cholesterol, albumin, alkaline phosphatase (ALP), alanine aminotransferase (ALT) and decreased levels of blood urea nitrogen and total bilirubin in alcohol-exposed male and female groups compared to controls. Brain water weight was not affected by alcohol exposure, though males tended to have slightly more water weight overall. Alcohol exposure led to reductions in tissue levels of glutathione in both the hippocampus and mFC which may indicate increased oxidative stress. Combined, these results suggest that hepatic encephalopathy does not appear to play a significant role in the neurotoxicity observed following alcohol exposure in this model.

Original languageEnglish (US)
Pages (from-to)35-40
Number of pages6
JournalNeurotoxicology and Teratology
Volume56
DOIs
StatePublished - Jul 1 2016

Fingerprint

Hepatic Encephalopathy
Alcohols
Frontal Lobe
Brain
Glutathione
Hippocampus
Weights and Measures
Alcoholic Intoxication
Blood
Water
Blood Urea Nitrogen
Brain Edema
Hypercholesterolemia
Alanine Transaminase
Bilirubin
Causality
Inhalation
Alcoholism
Oxidative stress
Alkaline Phosphatase

Keywords

  • Brain damage
  • Hepatic encephalopathy
  • Neurotoxicity
  • Oxidative stress
  • Vapor inhalation

ASJC Scopus subject areas

  • Developmental Neuroscience
  • Cellular and Molecular Neuroscience
  • Toxicology

Cite this

A neurotoxic alcohol exposure paradigm does not induce hepatic encephalopathy. / Hashimoto, Joel G.; Wiren, Kristine; Wilhelm, Clare.

In: Neurotoxicology and Teratology, Vol. 56, 01.07.2016, p. 35-40.

Research output: Contribution to journalArticle

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