Leukotrienes increase blood-brain barrier permeability following intraparenchymal injections in rats

Abstract

To examine whether leukotrienes could increase blood–brain barrier permeability, rats were anesthetized and injected intravenously with Evans blue. Ten microliters of vehicle, of leukotrienes B 4 , C 4 , or E 4 , or of arachidonic acid was injected over 1 hour directly into the brain parenchyma. The percentage of the total surface area of Evans blue extravasation in a coronal section of brain centered on the injection site was then determined as an estimate of blood–brain barrier permeability. Leukotrienes B 4 , C 4 , and E 4 , and arachidonic acid all increased blood–brain barrier permeability, but this effect was lost when the total dose was reduced to 20 ng. Increased blood–brain barrier permeability induced by arachidonic acid could be prevented by pretreatment with the lipoxygenase inhibitor BW755C, but not with indomethacin. Leukotrienes may play a role in the development of increased blood–brain barrier permeability after cerebral injury.