Sera of elderly obstructive sleep apnea patients alter blood-brain barrier integrity in vitro: a pilot study

Obstructive sleep apnea syndrome (OSAS) is characterized by repeated episodes of hypoxia during the night. The severity of the disorder can be evaluated using an apnea-hypopnea index (AHI). The physiological consequences are mainly cardiovascular and neuronal dysfunctions. One hypothesis to explain such associated neurological disorders is disruption of the blood-brain barrier (BBB), which protects the brain from endovascular cytotoxic compounds. We selected two subgroups of volunteers from the PROOF cohort study (France), a group of patients suffering newly diagnosed severe OSAS (AHI>30/h) and a group showing no sleep apnea (AHI<5/h). We exposed a human in vitro BBB model of endothelial cells (HBEC-5i) with sera of patients with and without OSAS. After exposure, we measured the apparent BBB permeability as well as tight junction and ABC transporter expression using whole cell ELISA. We showed that after incubation with sera from OSAS patients, there was a loss of integrity in the human in vitro BBB model; this was reflected by an increase in permeability (43%; p<0.001) and correlated with a 50% and 40% decrease in tight junction protein expression of ZO-1 and claudin-5, respectively. At the same time, we observed an upregulation in Pgp protein expression (52%) and functionality, and a downregulation in BCRP expression (52%). Our results demonstrated that severe BBB disorder after exposure to sera from OSAS patients was reflected by an opening of the BBB.