title: Protective effects of isothiocyanates on blood-CSF barrier disruption induced by oxidative stress.
abstract: The choroid plexuses (CPs) form the blood-cerebrospinal fluid (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 that can impact CP function. This study examined the effects of isothiocyanates, an abundant component in cruciferous vegetables, on H(2)O(2)-induced BCSFB disruption and CP cell death in vitro. It further examined the potential role of a transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2), in isothiocyanate-induced protection. Sulforaphane (SF) significantly reduced H(2)O(2)-induced BCSFB disruption as assessed by transepithelial electrical resistance (29 ± 7% reduction vs. 92 ± 2% decrease in controls) and [(3)H]mannitol permeability. Allyl-isothiocyanate (AITC) had a similar protective effect. H(2)O(2)-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 h and not with acute exposure (1 h). The protective effects of SF and AITC were associated with Nrf2 nuclear translocation and upregulated expression of antioxidative systems regulated by Nrf2, including heme oxygenase-1, NAD(P)H quinine oxidoreductase, and cysteine/glutamate exchange transporter. Thus isothiocyanates, as diet or medicine, may be a method for protecting BCSFB in neurological disorders.
authors.affiliation: Department of Neurosurgery, Medical School, University of Michigan, Ann Arbor, MI 48109, USA. jmxxdrnx@umich.edu
authors.forename: Jianming
authors.initials: J
authors.lastname: Xiang
authors.forename: Gina N
authors.initials: GN
authors.lastname: Alesi
authors.forename: Ningna
authors.initials: N
authors.lastname: Zhou
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000502:physiology; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology*; D002460:Cell Line; D002478:Cells, Cultured; D002831:Choroid Plexus / Q000166:cytology / Q000187:drug effects* / Q000503:physiopathology; D006861:Hydrogen Peroxide / Q000009:adverse effects / Q000494:pharmacology; D066298:In Vitro Techniques; D017879:Isothiocyanates / Q000494:pharmacology*; D023421:Models, Animal; D051267:NF-E2-Related Factor 2 / Q000502:physiology; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D013454:Sulfoxides; D013861:Thiocyanates; C041942:2,3,4-tri-O-acetylarabinopyranosyl isothiocyanate; D006861:Hydrogen Peroxide; C016766:sulforaphane