Intracarotid Infusion of Leukotriene C4 Selectively Increases Blood-Brain Barrier Permeability after Focal Ischemia in Rats

Abstract

Intracarotid infusions of leukotriene C₄ (LTC₄) were used to open selectively the blood–brain barrier (BBB) in ischemic tissue after middle cerebral artery (MCA) occlusion in rats. BBB permeability was determined by quantitative autoradiography using [¹⁴C]aminoisobutyric acid. Seventy-two hours after MCA occlusion, LTC₄ (4 μg total dose) infused into the carotid artery ipsilateral to the MCA occlusion selectively increased the unidirectional transfer constant for permeability K₁ approximately threefold within core ischemic tissue and tissue adjacent to the ischemic core. No effect on BBB permeability was seen within nonischemic brain tissue or in ischemic tissue after only 24 h after MCA occlusion. γ-Glutamyl transpeptidase (γ-GTP) activity was decreased in capillaries in ischemic tissue at 48 and 72 h after infarction, compared to high γ-GTP in normal brain capillaries and moderate γ-GTP in capillaries in the ischemic tissue at 24 h after infarction. These findings suggest that normal brain capillaries resist the vasogenic effects of LTC₄. In contrast, LTC₄ increases permeability in capillaries of ischemic tissue, where γ-GTP is decreased. γ-Glutamyl transpeptidase, an enzyme that inactivates LTC₄ to LTD₄ and LTE₄ to LTF₄, may act as an “enzymatic barrier” in normal brain capillaries to leukotrienes.