Effects of Leukotriene C4 and Acivicin on the Blood-Brain Barrier Permeability of Ischemic Rat Brains: Proof of Existence of Enzymatic Barrier

Abstract

We previously demonstrated that leukotriene C4 (LTC4) infused into the carotid artery ipsilateral to an experimental glial tumor increased the unidirectional transfer constant for permeability, Ki, two-fold within the tumor while no effect on permeability was seen in the normal brain [2]. Normal brain capillaries are rich in γ-glutamyl transpeptidase (γ-GTP), an enzyme which inactivates LTC4. In contrast, γ-GTP was absent in tumor capillaries. We suggested that normal brain capillaries may resist the vasogenic effects of LTC4, and hypothesized that this could relate to the ability of γ-GTP to act as an “enzymatic barrier” and inactivate leukotrienes in normal brain capillaries. We further speculated that leukotrienes could be important mediators of capillary permeability in pathological conditions where the ability of brain capillaries to inactivate LTC4 is impaired. To support this hypothesis, we already showed the ability of intracarotid infusions of LTC4 to selectively open the blood-brain barrier (BBB) in the ischemic tissue of the middle cerebral artery (MCA)-occluded rats [1]. Here, we further present the effects of leukotrienes on BBB permeability in ischemic tissue with or without acivicin, inhibitor of γ-GTP.