PMID- 30680941
OWN - NLM
STAT- MEDLINE
DCOM- 20201009
LR  - 20210109
IS  - 1755-5949 (Electronic)
IS  - 1755-5930 (Print)
IS  - 1755-5930 (Linking)
VI  - 25
IP  - 6
DP  - 2019 Jun
TI  - Propofol improved hypoxia-impaired integrity of blood-brain barrier via 
      modulating the expression and phosphorylation of zonula occludens-1.
PG  - 704-713
LID - 10.1111/cns.13101 [doi]
AB  - AIMS: 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. METHODS: 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-1alpha (HIF-1alpha) and vascular endothelial 
      growth factor (VEGF) expression, intracellular calcium concentration and Ca(2+) 
      /calmodulin-dependent protein kinase II (CAMKII) activation were measured. 
      RESULTS: 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-1alpha 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-alpha 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. CONCLUSION: Propofol 
      could protect against hypoxia-mediated impairment of BBB integrity. The 
      underlying mechanisms may involve the expression and phosphorylation of ZO-1.
CI  - (c) 2019 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & 
      Sons Ltd.
FAU - Chen, Wei
AU  - Chen W
AD  - Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, 
      China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Ju, Xing-Zhu
AU  - Ju XZ
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
AD  - Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, 
      Shanghai, China.
FAU - Lu, Yan
AU  - Lu Y
AD  - Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, 
      China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Ding, Xiao-Wei
AU  - Ding XW
AD  - Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, 
      China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Miao, Chang-Hong
AU  - Miao CH
AD  - Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, 
      China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
FAU - Chen, Jia-Wei
AU  - Chen JW
AUID- ORCID: 0000-0003-3726-9823
AD  - Department of Anesthesiology, Fudan University Shanghai Cancer Center, Shanghai, 
      China.
AD  - Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190124
PL  - England
TA  - CNS Neurosci Ther
JT  - CNS neuroscience & therapeutics
JID - 101473265
RN  - 0 (Cardiovascular Agents)
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Tjp1 protein, mouse)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (Zonula Occludens-1 Protein)
RN  - 0 (vascular endothelial growth factor A, mouse)
RN  - SY7Q814VUP (Calcium)
RN  - YI7VU623SF (Propofol)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/metabolism
MH  - Blood-Brain Barrier/*drug effects/metabolism
MH  - Calcium/metabolism
MH  - Cardiovascular Agents/*pharmacology
MH  - Cell Hypoxia/*drug effects/physiology
MH  - Cells, Cultured
MH  - Coculture Techniques
MH  - Endothelial Cells/drug effects/metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/antagonists & inhibitors/metabolism
MH  - Mice
MH  - Microvessels/drug effects/metabolism
MH  - Phosphorylation/drug effects
MH  - Propofol/*pharmacology
MH  - Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism
MH  - Zonula Occludens-1 Protein/*metabolism
PMC - PMC6515893
OTO - NOTNLM
OT  - blood-brain barrier
OT  - hypoxia
OT  - mouse brain microvascular endothelial cells
OT  - propofol
OT  - zonula occludens-1
COIS- The authors declare no conflict of interest.
EDAT- 2019/01/27 06:00
MHDA- 2020/10/10 06:00
PMCR- 2019/01/24
CRDT- 2019/01/26 06:00
PHST- 2018/10/31 00:00 [received]
PHST- 2018/12/04 00:00 [revised]
PHST- 2017/12/20 00:00 [accepted]
PHST- 2019/01/27 06:00 [pubmed]
PHST- 2020/10/10 06:00 [medline]
PHST- 2019/01/26 06:00 [entrez]
PHST- 2019/01/24 00:00 [pmc-release]
AID - CNS13101 [pii]
AID - 10.1111/cns.13101 [doi]
PST - ppublish
SO  - CNS Neurosci Ther. 2019 Jun;25(6):704-713. doi: 10.1111/cns.13101. Epub 2019 Jan 
      24.