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.

Activating the Nrf2-mediated antioxidant response element restores barrier function in the alveolar epithelium of HIV-1 transgenic rats

“…Sulforaphane ingested orally has been shown to induce phase II enzymes such as glutathione-S-transferase, NQO1, and hemoxygenase-1 (HO-1) in the human upper airway (39). Other studies have shown that, following traumatic brain injury, early sulforaphane treatment upregulates Nrf2-dependent genes for GST and HO-1, attenuates the loss of expression of the tight junction proteins occludin and claudin-5, reduces endothelial cell death, and preserves blood-brain barrier function (12,43,44). In the blood-brain barrier, enhancing the expression of Nrf2-driven genes with a specific peptide that binds to Keap1 and releases Nrf2 into the nuclear compartment significantly reduced endothelial barrier compromise after traumatic brain injury (45).…”

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

“…Of importance, cytoprotective transporters and enzymes are under the transcriptional regulation of nuclear factors, which are expressed in the choroid plexuses [73]. The nuclear factor erythroid 2-related factor 2 pathway, in particular, represents an attractive target to protect the BCSFB and induce its antioxidant capacities in neurological disorders associated with oxidative stress [168].…”

Neuroprotection by 6-(methylsulfinyl)hexyl isothiocyanate in a 6-hydroxydopamine mouse model of Parkinson׳s disease

“…Even more interesting, recent findings demonstrated that 6-MSITC provided neuroprotection against cytotoxicity induced by oxidative stress in rat striatal cultures by raising the intracellular GSH content (Mizuno et al, 2011). Although other isothiocyanates have shown interesting neuroprotective effects Tarozzi et al, 2012;Xiang et al, 2012), to the best of our knowledge, no studies have been done before on the 6-MSITC neuroprotective activity in an in vivo PD model.…”