Neurovascular protection of cilostazol in stroke-prone spontaneous hypertensive rats associated with angiogenesis and pericyte proliferation

Yoshio Omote, Kentaro Deguchi, Syoichiro Kono, Ning Liu, Wentao Liu, Tomoko Kurata, Toru Yamashita, Yoshio Ikeda, Koji Abe

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)369-374
Number of pages6
JournalJournal of Neuroscience Research
Volume92
Issue number3
DOIs
Publication statusPublished - Mar 2014

Fingerprint

Pericytes
Stroke
Vascular Endothelial Growth Factor Receptor-2
clopidogrel
Platelet Aggregation Inhibitors
Matrix Metalloproteinase 9
Aspirin
Cerebral Infarction
Inbred SHR Rats
Gelatin
Activities of Daily Living
Cognition
cilostazol
Cause of Death
Endothelial Cells
Brain

Keywords

  • Angiogenesis
  • Cerebral infarction
  • Cilostazol
  • Neurovascular unit
  • SHR-SP

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience

Cite this

Neurovascular protection of cilostazol in stroke-prone spontaneous hypertensive rats associated with angiogenesis and pericyte proliferation. / Omote, Yoshio; Deguchi, Kentaro; Kono, Syoichiro; Liu, Ning; Liu, Wentao; Kurata, Tomoko; Yamashita, Toru; Ikeda, Yoshio; Abe, Koji.

In: Journal of Neuroscience Research, Vol. 92, No. 3, 03.2014, p. 369-374.

Research output: Contribution to journalArticle

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