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.
Keywords: Aquaporin, Blood brain barrier (BBB), Inducible nitric oxide synthase (iNOS), Inflammation, Matrix
metalloproteinase (MMP), Oleic acid.
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