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CNS Neurosci Ther. 2019 Jun;25(6):704-713. doi: 10.1111/cns.13101. Epub 2019 Jan 24.

Propofol improved hypoxia-impaired integrity of blood-brain barrier via modulating the expression and phosphorylation of zonula occludens-1.

Chen W1,2, Ju XZ2,3, Lu Y1,2, Ding XW1,2, Miao CH1,2, Chen JW1,2.

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Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.



Hypoxia may damage blood-brain barrier (BBB). The neuroprotective effect of propofol has been reported. We aimed to identify whether and how propofol improved hypoxia-induced impairment of BBB integrity.


Mouse brain microvascular endothelial cells (MBMECs) and astrocytes were cocultured to establish in vitro BBB model. The effects of hypoxia and propofol on BBB integrity were examined. Further, zonula occludens-1 (ZO-1) expression and phosphorylation, hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) expression, intracellular calcium concentration and Ca2+ /calmodulin-dependent protein kinase II (CAMKII) activation were measured.


Hypoxia-impaired BBB integrity, which was protected by propofol. Hypoxia-reduced ZO-1 expression, while induced ZO-1 phosphorylation. These effects were attenuated by propofol. The expression of HIF-1α and VEGF was increased by hypoxia and was alleviated by propofol. The hypoxia-mediated suppression of ZO-1 and impaired BBB integrity was reversed by HIF-α inhibitor and VEGF inhibitor. In addition, hypoxia increased the intracellular calcium concentration and induced the phosphorylation of CAMKII, which were mitigated by propofol. The hypoxia-induced phosphorylation of ZO-1 and impaired BBB integrity was ameliorated by calcium chelator and CAMKII inhibitor.


Propofol could protect against hypoxia-mediated impairment of BBB integrity. The underlying mechanisms may involve the expression and phosphorylation of ZO-1.


blood-brain barrier; hypoxia; mouse brain microvascular endothelial cells; propofol; zonula occludens-1

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