Inhibition of the increased permeability of blood-brain barrier in escherichia coli-induced meningitis by carboxyfullerene

The effect of a water-soluble trimalonic acid derivative of fullerene, carboxyfullerene (C₆₃(COOH)₆), on the opening of blood-brain barrier (BBB) in Escherichia coli (E. coli)-induced meningitis was tested. In E. coli-induced meningitis model, the increase of BBB permeability was manifested in two distinct phases based on cytokine expression pattern and neutrophilic infiltration in B6 mice. An early increase in BBB permeability was occurred at 1-5 h post injection that could be blocked by either anti-TNF-α or anti-IL-1β antibodies. A late one (neutrophil-associated BBB opening) was manifested at 6-12 h that was inhibited by vinblastine pretreatment. Inhibition of the early E. coli-induced BBB opening blocked the development of the late one. Furthermore, the neutrophil-associated BBB opening (the late phase), but not cytokine-induced one (the early phase), was inhibited by a water-soluble carboxyfullerene.