High levels of free fatty acids (FFAs) are a contributing pathogenic factor in many diseases like acute lung injury and tumor growth. In fat embolism, which most commonly occurs following trauma, orthopaedic surgery of hypoxic-ischemic brain injuries, FFAs is toxic in tissue damage by the blood brain barrier (BBB) breakdown. Oleic acid is the most important constituent acid in human fat and more toxic than other fatty acid in cerebral damage. We have investigated the permeability changes of BBB and the role of free radical and neutrophil in brain injury from fat embolism by oleic acid injuction into the rat carotid artery. The changes of BBB measured using two tracers (FITC-dextran and Evans blue) and the endothelial barrier antigen (EBA) as a specific marker for the BBB physiological function in rats. Immunohistochmistry was performed using myeloperoxidase (MPO, neutrophil marker), intracellur adression molecule-1 (ICAM-1), nitrotyrosine, inducible NOS (iNOS) and endothelial NOS (eNOS) at 2 h, 6 h and 24 h after oleic acid injection. The increases of two tracers and the decrease of EBA indicated dysfunction of BBB by oleic acid administration. Oleic acid produced expression of MPO, ICAM-1 and nitrotyrosine and overexpression iNOS and eNOS at 2 h, 6 h and 24 h after injuction. These results suggest that oleic acid induces dysfunction of the BBB and activated neutrophils play a major role in the BBB breakdown by the formation of free radical like peroxynitrite and nitric oxide.
Source: Korean Journal of Physiology & Pharmacology.2005 Oct;9(Suppl I):S88-S88
|