PMID- 24375726
OWN - NLM
STAT- MEDLINE
DCOM- 20140910
LR  - 20220223
IS  - 1097-4547 (Electronic)
IS  - 0360-4012 (Linking)
VI  - 92
IP  - 3
DP  - 2014 Mar
TI  - Neurovascular protection of cilostazol in stroke-prone spontaneous hypertensive 
      rats associated with angiogenesis and pericyte proliferation.
PG  - 369-74
LID - 10.1002/jnr.23327 [doi]
AB  - Stroke is the major cause of death and decrease in the activities of daily 
      living. This study sought to evaluate the effects of commonly used antiplatelet 
      drugs on spontaneous cerebral infarction in relation to neurovascular protection 
      associated with angiogenesis and pericyte proliferation. Stroke-prone 
      spontaneously hypertensive rats (SHR-SP) were treated with vehicle, aspirin, 
      clopidogrel, or cilostazol from 8 to 10 weeks of age. The interaction of 
      neurovascular components among endothelial cells, pericytes, and astrocytic 
      endfeet were immunohistochemically examined in brain sections. Angiogenesis 
      associated with vascular endothelial growth factor receptor 2 (VEGFR2) and 
      pericyte proliferation were also examined immunohistochemically. The expression 
      and activity of matrix metalloproteinase 9 (MMP-9) were assessed 
      immunohistochemically and by gelatin zymography. Among the antiplatelet drugs, 
      cilostazol preserved the neurovascular unit (NVU) by preventing astrocytic 
      endfeet or pericytes from pathological detachment found in the vehicle and 
      aspirin treatment. Cilostazol also inhibited the expression and activity of 
      MMP-9, which led to protection of the NVU. Furthermore, in the periinfarct area, 
      cilostazol increased VEGFR2 expression, promoting angiogenesis through 
      proliferation of pericytes. The present study showed a strong protection of NVU 
      integrity by cilostazol and the promotion of angiogenesis by stimulating both 
      endothelial VEGFR2 expression and pericyte proliferation. In addition to the 
      antioxidative effect, these pleiotropic effects of cilostazol contribute to 
      reduce spontaneous infarct volume and preserve motor and cognitive function in 
      SHR-SP.
CI  - Copyright (c) 2013 Wiley Periodicals, Inc.
FAU - Omote, Yoshio
AU  - Omote Y
AD  - Department of Neurology, Graduate School of Medicine, Dentistry and 
      Pharmaceutical Sciences, Okayama University, Okayama, Japan.
FAU - Deguchi, Kentaro
AU  - Deguchi K
FAU - Kono, Syoichiro
AU  - Kono S
FAU - Liu, Ning
AU  - Liu N
FAU - Liu, Wentao
AU  - Liu W
FAU - Kurata, Tomoko
AU  - Kurata T
FAU - Yamashita, Toru
AU  - Yamashita T
FAU - Ikeda, Yoshio
AU  - Ikeda Y
FAU - Abe, Koji
AU  - Abe K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20131221
PL  - United States
TA  - J Neurosci Res
JT  - Journal of neuroscience research
JID - 7600111
RN  - 0 (Antigens)
RN  - 0 (Fibrinolytic Agents)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Proteoglycans)
RN  - 0 (Tetrazoles)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 0 (chondroitin sulfate proteoglycan 4)
RN  - A74586SNO7 (Clopidogrel)
RN  - EC 2.7.10.1 (Vascular Endothelial Growth Factor Receptor-2)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - N7Z035406B (Cilostazol)
RN  - OM90ZUW7M1 (Ticlopidine)
RN  - R16CO5Y76E (Aspirin)
SB  - IM
MH  - Animals
MH  - Antigens/metabolism
MH  - Aspirin/therapeutic use
MH  - Cerebrovascular Circulation/drug effects
MH  - Cilostazol
MH  - Clopidogrel
MH  - Disease Models, Animal
MH  - Endothelium/pathology
MH  - Fibrinolytic Agents/pharmacology/*therapeutic use
MH  - Male
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Neovascularization, Pathologic/etiology/*prevention & control
MH  - Nerve Tissue Proteins/metabolism
MH  - Pericytes/*drug effects
MH  - Proteoglycans/metabolism
MH  - Rats
MH  - Rats, Inbred SHR
MH  - Stroke/etiology/*prevention & control
MH  - Tetrazoles/pharmacology/*therapeutic use
MH  - Ticlopidine/analogs & derivatives/therapeutic use
MH  - Vascular Endothelial Growth Factor A/metabolism
MH  - Vascular Endothelial Growth Factor Receptor-2/metabolism
OTO - NOTNLM
OT  - SHR-SP
OT  - angiogenesis
OT  - cerebral infarction
OT  - cilostazol
OT  - neurovascular unit
EDAT- 2014/01/01 06:00
MHDA- 2014/09/11 06:00
CRDT- 2013/12/31 06:00
PHST- 2013/06/21 00:00 [received]
PHST- 2013/09/12 00:00 [revised]
PHST- 2013/10/23 00:00 [accepted]
PHST- 2013/12/31 06:00 [entrez]
PHST- 2014/01/01 06:00 [pubmed]
PHST- 2014/09/11 06:00 [medline]
AID - 10.1002/jnr.23327 [doi]
PST - ppublish
SO  - J Neurosci Res. 2014 Mar;92(3):369-74. doi: 10.1002/jnr.23327. Epub 2013 Dec 21.