Disruption of the blood–brain barrier during TNBS colitis

Abstract

Well-documented central nervous system changes during colitis suggest possible alterations of blood-brain barrier (BBB) permeability, yet the integrity of the BBB has not been fully evaluated in experimental colitis. Our aim was to investigate whether trinitrobenzene sulphonic acid (TNBS) colitis was associated with an increase in the permeability of the BBB. Sprague-Dawley rats were given an intracolonic injection of saline or TNBS and studied 1, 2, 3, 7 and 21 days after treatment. The extravasation of endogenous immunoglobulin G, a large molecule, was not altered at any time after TNBS treatment. In contrast, significant increases in the BBB leakage of sodium fluorescein, a much smaller molecule, were observed 1 and 2 days after the induction of colitis, in and around the circumventricular organs; the organum vasculosum of the lamina terminalis, subfornical organ and median eminence of the hypothalamus. TNBS-treated rats also exhibited sodium fluorescein leakage in focal areas in the brain parenchyma. The expression of endothelial barrier antigen, a protein associated with the BBB, was reduced about 60% 48 h after the induction of colitis. This returned to control values by 3 weeks, when colitis had largely subsided. In conclusion, experimental colitis transiently increased permeability of the brain to small molecules through a mild disruption of the BBB.