Transient blood brain barrier disruption induced by oleic acid is mediated by nitric oxide

Hyung Soo Han, Jae Hee Jang, Jae Sik Park, Hak Jin Kim, Jong Kun Kim

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

The blood brain barrier (BBB) maintains cerebral microenvironmental homeostasis. Transient disruption of the BBB after brain fat embolism in clinical cases and animal models has been reported but the precise mechanism underlying this occurrence is unclear. In the present study, we investigated BBB alterations in rats treated oleic acid (OA) delivered intra-arterially. Following OA treatment, transient brain edema, extravasation of Evans blue and Fluorescein isothiocyanate (FITC)-labeled dextran, and loss of laminin in the affected brain area were observed. Activation of matrix metalloproteinase (MMP)-2, -3, and -13 was found in the cerebral vessels 2 h after OA administration. Expression of intercellular adhesion molecule (ICAM)-1 in the vessels and neutrophil infiltration into the brain tissue was also observed. Inducible nitric oxide synthase (iNOS) was expressed in the neutrophils and nitrotyrosine was produced mainly in the vessels. Inhibitor of iNOS activity suppressed the loss of laminin, leakage of FITC-labeled dextran and Evans blue, and activation of MMP-2 and -13. Protein level of aquaporin (AQ)-4 was increased after OA administration but was not affected by treatment with iNOS inhibitor. In conclusion, we suggest that nitric oxide (NO) contributes to OA-induced MMP activation, BBB disruption and the development of transient brain edema.

Original languageEnglish
Pages (from-to)287-296
Number of pages10
JournalCurrent Neurovascular Research
Volume10
Issue number4
DOIs
StatePublished - Nov 2013

Keywords

  • Aquaporin
  • Blood brain barrier (BBB)
  • Inducible nitric oxide synthase (iNOS)
  • Inflammation
  • Matrix metalloproteinase (MMP)
  • Oleic acid

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