Viability of microvascular endothelial cells to direct exposure of formalin, λ-carrageenan, and complete Freund's adjuvant

Jason D. Huber, Vincent S. Hau, Karen S. Mark, Rachel C. Brown, Chris R. Campos, Thomas P. Davis

Research output: Contribution to journalArticle

10 Scopus citations

Abstract

We investigated three inflammatory agents to establish if these substances elicit a direct effect on the functional and structural integrity of the blood-brain barrier. Cellular cytotoxicity and paracellular permeability were assessed in vitro using primary bovine brain microvascular endothelial cells exposed to formalin, λ-carrageenan, or complete Freund's adjuvant for 1, 3, or 72 h, respectively. Results showed that only the highest concentration (0.025%) of formalin produced a decrease in cell viability (∼34%) and a significant increase in cell permeability to [14C]sucrose at 120 min (∼137%). Brain perfusion using female Sprague-Dawley rats showed no difference in paracellular permeability to [14C]sucrose for any inflammatory agent. Western blot analyses were performed on isolated rat brain microvessels to assess the structural integrity of blood-brain barrier tight junctions. Results indicate that expression of zonula occludens-1, occludin, claudin-1, and actin remain unchanged following intravenous exposure to inflammatory agents. This study confirms that changes seen at the blood-brain barrier following a peripheral inflammation are due to physiological responses to the given inflammatory agent and not to any direct interaction between the inflammatory agent and the brain microvasculature.

Original languageEnglish (US)
Pages (from-to)297-304
Number of pages8
JournalEuropean Journal of Pharmacology
Volume450
Issue number3
DOIs
StatePublished - Aug 30 2002

Keywords

  • Blood-brain barrier
  • Inflammation
  • Occludin
  • Pain
  • Tight junctions
  • Zonula occludens-1

ASJC Scopus subject areas

  • Pharmacology

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