The choroid plexuses (CPs) form the blood-CSF barrier (BCSFB) and play an important role in maintaining brain normal function and the brain response to injury. Many neurological disorders are associated with oxidative stress which can impact CP function. This study examined the effects of isothiocyanates, an abundant component in cruciferous vegetables, on H2O2-induced BCSFB disruption and CP cell death in vitro. It further examined the potential role of a transcription factor, Nrf2, in isothiocyanate-induced protection. Sulforaphane (SF) significantly reduced H2O2-induced BCSFB disruption as assessed by transepithelial electrical resistance (29±7% reduction vs. 92±2% decrease in controls) and [3H]mannitol permeability. Allyl-isothiocyanate (AITC) had a similar protective effect. H2O2-induced induced epithelial cell death was also reduced by these isothiocyanates. In primary CP cells, SF and AITC reduced cell death by 42±3 and 53±10%, respectively. Similar protection was found in a CP cell line, Z310. Protection was only found with pretreatment for 12-48 hours and not with acute exposure (1 hour). The protective effects of SF and AITC were associated with Nrf2 nuclear translocation and upregulated expression of antioxidative systems regulated by Nrf2, including HO-1, NQO1 and xCT. Thus, isothiocyanates, as diet or medicine, may be a method for protecting BCSFB in neurological disorders.
- choroid plexus
- blood-CSF barrier
- oxidative stress
- Copyright © 2011, American Journal of Physiology - Regulatory, Integrative and Comparative Physiology