Fructose‐1,6‐diphosphate restores the inflammation‐induced permeability changes in brain microvascular endothelial cell

Abstract

The blood-brain barrier (BBB) impedes the influx of un-wanted substances from blood milieu to brain, which is necessary for the maintenance and regulation of the neural microenvironment. Dysfunction of BBB has been implicated in the pathogenesis of a variety of CNS diseases such as stroke and Alzheimer¡¯s disease. Thus, the control of the barrier properties has been regarded as one of the critical issues for the treatment of various cerebral diseases. F1,6DP, a glycolytic intermediate, is reported to protect neuronal cell death against oxidative stress, excitotoxic injury, beta amyloid-induced neurotoxicity and ischemic insult. However, the neuroprotective mechanisms of F1,6DP are not fully understood. In this study, we examined the effect of F1,6DP on the permeability of BBB under inflammatory conditions. Firstly, we established in vitro BBB model using bEnd.3 and primary cultured mouse astrocyte (PA). This coculture model is comparable to well-known HUVEC-C6 coculture system in terms of permeability criteria such as transendothelial electrical resistance (TEER) and permeability coefficients of sucrose and propranolol. Inflammatory stimuli such as LPS and TNFa decreased TEER and increased the permeability coefficient of sucrose. F1,6DP restored the changes in TEER and permeability coefficients induced by inflammatory stimuli. And also, F1,6DP reversed the alterations in the distribution of the endothelial tight junction (TJ) proteins- occludin and ZO-1 which were diffused throughout the cytoplasm in the presence of LPS. These results suggest that F1,6DP could restore the function of BBB altered by inflammation through maintenance the junctional integrity of BBB This study was supported, in part, by Gyunggi-do through CCRB-GRRC.