Altered expression of zonula occludens-2 precedes increased blood-brain barrier permeability in a murine model of fulminant hepatic failure

Naoki Shimojima, Christopher B. Eckman, Michael McKinney, Daniel Sevlever, Satoshi Yamamoto, Wenlang Lin, Dennis W. Dickson, Justin H. Nguyen

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Brain edema secondary to increased blood-brain barrier (BBB) permeability is a lethal complication in fulminant hepatic failure (FHF). Intact tight junctions (TJ) between brain capillary endothelial cells are critical for normal BBB function. However, the role of TJ in FHF has not been explored. We hypothesized that alterations in the composition of TJ proteins would result in increased BBB permeability in FHF. In this study, FHF was induced in C57BL/6J mice by using azoxymethane. BBB permeability was assessed with sodium fluorescein. Expression of TJ proteins was determined by Western blot, and their cellular distribution was examined using immunofluorescent microscopy. Comatose FHF mice had significant cerebral sodium fluorescein extravasation compared with control and precoma FHF mice, indicating increased BBB permeability. Western blot analysis showed a significant decrease in zonula occludens (ZO)-2 expression starting in the precoma stage. Immunofluorescent microscopy showed a significantly altered distribution pattern of ZO-2 in isolated microvessels from precoma FHF mice. These changes were more prominent in comatose FHF animals. Significant alterations in ZO-2 expression and distribution in the tight junctions preceded the increased BBB permeability in FHF mice. These results suggest that ZO-2 may play an important role in the pathogenesis of brain edema in FHF.

Original languageEnglish
Pages (from-to)101-108
Number of pages8
JournalJournal of Investigative Surgery
Volume21
Issue number3
DOIs
Publication statusPublished - 2008 May
Externally publishedYes

Fingerprint

Acute Liver Failure
Tight Junctions
Blood-Brain Barrier
Permeability
Tight Junction Proteins
Brain Edema
Coma
Fluorescein
Microscopy
Western Blotting
Azoxymethane
Microvessels
Inbred C57BL Mouse
Endothelial Cells

Keywords

  • Acute liver failure
  • Blood-brain barrier permeability
  • Brain edema
  • Tight junction
  • ZO-2

ASJC Scopus subject areas

  • Surgery

Cite this

Altered expression of zonula occludens-2 precedes increased blood-brain barrier permeability in a murine model of fulminant hepatic failure. / Shimojima, Naoki; Eckman, Christopher B.; McKinney, Michael; Sevlever, Daniel; Yamamoto, Satoshi; Lin, Wenlang; Dickson, Dennis W.; Nguyen, Justin H.

In: Journal of Investigative Surgery, Vol. 21, No. 3, 05.2008, p. 101-108.

Research output: Contribution to journalArticle

Shimojima, Naoki ; Eckman, Christopher B. ; McKinney, Michael ; Sevlever, Daniel ; Yamamoto, Satoshi ; Lin, Wenlang ; Dickson, Dennis W. ; Nguyen, Justin H. / Altered expression of zonula occludens-2 precedes increased blood-brain barrier permeability in a murine model of fulminant hepatic failure. In: Journal of Investigative Surgery. 2008 ; Vol. 21, No. 3. pp. 101-108.
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