RESEARCH ARTICLE Fructose-1,6-bisphosphate ameliorates lipopolysaccharideinduced dysfunction of blood–brain barrier

Fructose-1,6-bisphosphate (FBP), a glycolyticintermediate, has neuroprotective effects in various braininjury models. However, its effects on blood–brain barrier(BBB) are largely unknown. In this study, we investigatedthe effects of FBP on lipopolysaccharide (LPS)-inducedBBB dysfunction in in vitro BBB model comprising cocultureof mouse brain endothelial cell line, bEnd.3 andmouse primary astrocyte and explored its action mechanismtherein involved. LPS induced the impairment of endothelialpermeability and transendothelial electrical resistance(TEER). The functional changes were confirmed by alterationsin immunostaining for junctional proteins occludin,ZO-1 and VE-cadherin, such as the loss of cortical stainingpattern and appearance of intercellular gaps in endothelialcells. Co-administration of FBP alleviated the deleteriouseffects of LPS on BBB permeability and TEER in a dosedependent manner. And also FBP inhibited the LPS-inducedchanges in the distribution of endothelial junctional proteins,resulting in the better preservation of monolayer integrity. FBP suppressed the production of reactive oxygen species(ROS) but did not affect cyclooxygenase-2 expression andprostaglandin E2 production in endothelial cells stimulatedwith LPS. Taken together, these data suggest that FBP couldameliorate LPS-induced BBB dysfunction through themaintenance of junctional integrity, which might be mediatedby downregulation of ROS production. KCI Citation Count: 19