PMID- 24472843
OWN - NLM
STAT- MEDLINE
DCOM- 20150122
LR  - 20181202
IS  - 1095-9327 (Electronic)
IS  - 1044-7431 (Linking)
VI  - 60
DP  - 2014 May
TI  - Cilostazol attenuates ischemia-reperfusion-induced blood-brain barrier 
      dysfunction enhanced by advanced glycation endproducts via transforming growth 
      factor-beta1 signaling.
PG  - 1-9
LID - S1044-7431(14)00007-4 [pii]
LID - 10.1016/j.mcn.2014.01.006 [doi]
AB  - We investigated the effects of cilostazol, a selective inhibitor of 
      phosphodiesterase 3, on blood-brain barrier (BBB) integrity against 
      ischemia-reperfusion injury enhanced by advanced glycation endproducts (AGEs). We 
      used in vitro BBB models with primarily cultured BBB-related cells from rats 
      (brain capillary endothelial cells, astrocytes and pericytes), and subjected 
      cells to either normoxia or 3-h oxygen glucose deprivation (OGD)/24-h 
      reoxygenation with or without AGEs. Treatment of AGEs did not affect the 
      transendothelial electrical resistance (TEER) in the BBB model under normoxia, 
      but there was a significant decrease in TEER under 3-h OGD/24-h reoxygenation 
      conditions with AGEs. Cilostazol inhibited decreases in TEER induced by 3-h 
      OGD/24-h reoxygenation with AGEs. Immunocytochemical and Western blot analyses 
      showed that AGEs reduced the expression of claudin-5, the main functional protein 
      of tight junctions (TJs). In contrast, cilostazol increased the expression of 
      claudin-5 under 3-h OGD/24-h reoxygenation with AGEs. Furthermore, while AGEs 
      increased the production of extracellular transforming growth factor (TGF)-beta1, 
      cilostazol inhibited the production of extracellular TGF-beta1 and restored the 
      integrity of TJs. Thus, we found that AGEs enhanced ischemia-reperfusion injury, 
      which mainly included decreases in the expression of proteins comprising TJs 
      through the production of TGF-beta1. Cilostazol appeared to limit 
      ischemia-reperfusion injury with AGEs by improving the TJ proteins and inhibiting 
      TGF-beta1 signaling.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Takeshita, Tomonori
AU  - Takeshita T
AD  - Department of Neurosurgery, Nagasaki University Graduate School of Biomedical 
      Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
FAU - Nakagawa, Shinsuke
AU  - Nakagawa S
AD  - Department of Pharmacology, Nagasaki University Graduate School of Biomedical 
      Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; BBB Laboratory, 
      PharmaCo-Cell Company, Ltd., 1-43 Dejima, Nagasaki 850-0862, Japan. Electronic 
      address: shin3@nagasaki-u.ac.jp.
FAU - Tatsumi, Rie
AU  - Tatsumi R
AD  - Department of Pharmacology, Nagasaki University Graduate School of Biomedical 
      Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
FAU - So, Gohei
AU  - So G
AD  - Department of Neurosurgery, Nagasaki University Graduate School of Biomedical 
      Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
FAU - Hayashi, Kentaro
AU  - Hayashi K
AD  - Department of Neurosurgery, Nagasaki University Graduate School of Biomedical 
      Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
FAU - Tanaka, Kunihiko
AU  - Tanaka K
AD  - Department of Pharmacology, Nagasaki University Graduate School of Biomedical 
      Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan.
FAU - Deli, Maria A
AU  - Deli MA
AD  - Laboratory of Molecular Neurobiology, Institute of Biophysics, Biological 
      Research Center, Hungarian Academy of Sciences, Temesvari korut 62, H-6726 
      Szeged, Hungary.
FAU - Nagata, Izumi
AU  - Nagata I
AD  - Department of Neurosurgery, Nagasaki University Graduate School of Biomedical 
      Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
FAU - Niwa, Masami
AU  - Niwa M
AD  - Department of Pharmacology, Nagasaki University Graduate School of Biomedical 
      Sciences, 1-12-4 Sakamoto, Nagasaki 852-8523, Japan; BBB Laboratory, 
      PharmaCo-Cell Company, Ltd., 1-43 Dejima, Nagasaki 850-0862, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140125
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (Claudin-5)
RN  - 0 (Glycation End Products, Advanced)
RN  - 0 (Phosphodiesterase 3 Inhibitors)
RN  - 0 (Tetrazoles)
RN  - 0 (Transforming Growth Factor beta1)
RN  - N7Z035406B (Cilostazol)
SB  - IM
MH  - Animals
MH  - Astrocytes/drug effects/metabolism
MH  - Blood-Brain Barrier/*drug effects/metabolism
MH  - Capillary Permeability
MH  - *Cell Hypoxia
MH  - Cells, Cultured
MH  - Cilostazol
MH  - Claudin-5/genetics/metabolism
MH  - Electric Impedance
MH  - Glycation End Products, Advanced/*metabolism
MH  - Pericytes/drug effects/*metabolism
MH  - Phosphodiesterase 3 Inhibitors/*pharmacology
MH  - Rats
MH  - Rats, Wistar
MH  - Reperfusion Injury/metabolism
MH  - Signal Transduction
MH  - Tetrazoles/*pharmacology
MH  - Tight Junctions/drug effects/metabolism
MH  - Transforming Growth Factor beta1/*metabolism
OTO - NOTNLM
OT  - Advanced glycation endproducts
OT  - Blood-brain barrier
OT  - Cilostazol
OT  - Claudin-5
OT  - Oxygen glucose deprivation/reoxygenation
OT  - Transforming growth factor-beta
EDAT- 2014/01/30 06:00
MHDA- 2015/01/23 06:00
CRDT- 2014/01/30 06:00
PHST- 2013/10/30 00:00 [received]
PHST- 2013/12/19 00:00 [revised]
PHST- 2014/01/19 00:00 [accepted]
PHST- 2014/01/30 06:00 [entrez]
PHST- 2014/01/30 06:00 [pubmed]
PHST- 2015/01/23 06:00 [medline]
AID - S1044-7431(14)00007-4 [pii]
AID - 10.1016/j.mcn.2014.01.006 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2014 May;60:1-9. doi: 10.1016/j.mcn.2014.01.006. Epub 2014 Jan 
      25.