PMID- 34709593
OWN - NLM
STAT- MEDLINE
DCOM- 20220330
LR  - 20230905
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 39
IP  - 6
DP  - 2021 Dec
TI  - Opicapone Protects Against Hyperhomocysteinemia-Induced Increase in Blood-Brain 
      Barrier Permeability.
PG  - 2018-2028
LID - 10.1007/s12640-021-00429-8 [doi]
AB  - Hyperhomocysteinemia (HHcy)-related brain vascular disorders and brain 
      endothelial dysfunction are important characteristics of the pathogeneses of 
      subarachnoid hemorrhage and stroke. Upregulated homocysteine (Hcy) can impair the 
      integrity of the blood-brain barrier (BBB). Opicapone has been recently licensed 
      for the management of Parkinson's disease (PD); however, it is unknown whether it 
      possesses a protective effect in brain vessels against HHcy. To investigate the 
      beneficial effects of Opicapone on BBB permeability against HHcy, we carried out 
      both in vivo and in vitro experiments. Mice were allocated into four groups: the 
      Control, Opicapone, HHcy, and HHcy + Opicapone. Interestingly, we found that the 
      administration of Opicapone attenuated the increased BBB permeability in 
      Hcy-treated mice, as determined by sodium fluorescein staining. The 
      immunofluorescence staining showed that Opicapone prevented homocysteine-induced 
      reduction of claudin-2 in the mice cortices. The in situ zymography assay 
      revealed that Opicapone suppressed homocysteine-increased matrix 
      metalloproteinases (MMPs) activity in the cortices. In bEnd.3 brain endothelial 
      cells, Opicapone treatment ameliorated homocysteine-induced lactate dehydrogenase 
      (LDH) release and expression of matrix metalloproteinase-2 (MMP-2) and matrix 
      metalloproteinase-9 (MMP-9). Furthermore, Opicapone alleviated 
      homocysteine-induced decrease in claudin-2 level in bEnd.3 cells. In summary, our 
      results show that Opicapone protects against HHcy-induced BBB permeability by 
      reducing the expression and gelatinase activity of MMPs, and increasing the 
      expression of claudin-2.
CI  - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business 
      Media, LLC, part of Springer Nature.
FAU - Wang, Jian
AU  - Wang J
AD  - Department of Neurology, Ya'an Peoples Hospital, Ya'an, 625000, Sichuan, China.
FAU - Zheng, Bo
AU  - Zheng B
AD  - Department of Neurology, Ya'an Peoples Hospital, Ya'an, 625000, Sichuan, China.
FAU - Yang, Shu
AU  - Yang S
AD  - Department of Neurology, The Affiliated Hospital of University of Electronic 
      Science and Technology, Sichuan Provincial People's Hospital, Chengdu, 610000, 
      Sichuan, China.
FAU - Zheng, Hui
AU  - Zheng H
AD  - Department of Neurology, Chengdu First People's Hospital, Chengdu, 610000, 
      Sichuan, China. haoyun19882@163.com.
FAU - Wang, Jianhong
AU  - Wang J
AUID- ORCID: 0000-0001-6777-9299
AD  - Department of Neurology, The Affiliated Hospital of University of Electronic 
      Science and Technology, Sichuan Provincial People's Hospital, Chengdu, 610000, 
      Sichuan, China. drwang_jh652@163.com.
LA  - eng
GR  - 2019ZYZF0063, 2020yj0497, and 2019yyjskf06/the science and technology ministry of 
      sichuan province/
PT  - Journal Article
DEP - 20211028
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Oxadiazoles)
RN  - Y5929UIJ5N (opicapone)
SB  - IM
MH  - Animals
MH  - Blood-Brain Barrier/*drug effects
MH  - Blotting, Western
MH  - Cell Membrane Permeability/drug effects
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Hyperhomocysteinemia/*complications
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Neuroprotective Agents/pharmacology/*therapeutic use
MH  - Oxadiazoles/pharmacology/*therapeutic use
MH  - Real-Time Polymerase Chain Reaction
OTO - NOTNLM
OT  - Blood-brain barrier
OT  - Hyperhomocysteinemia
OT  - MMP-9
OT  - Opicapone
EDAT- 2021/10/29 06:00
MHDA- 2022/03/31 06:00
CRDT- 2021/10/28 12:35
PHST- 2021/07/21 00:00 [received]
PHST- 2021/10/06 00:00 [accepted]
PHST- 2021/09/28 00:00 [revised]
PHST- 2021/10/29 06:00 [pubmed]
PHST- 2022/03/31 06:00 [medline]
PHST- 2021/10/28 12:35 [entrez]
AID - 10.1007/s12640-021-00429-8 [pii]
AID - 10.1007/s12640-021-00429-8 [doi]
PST - ppublish
SO  - Neurotox Res. 2021 Dec;39(6):2018-2028. doi: 10.1007/s12640-021-00429-8. Epub 
      2021 Oct 28.