title: Clinical and pathological improvement in stroke-prone spontaneous hypertensive rats related to the pleiotropic effect of cilostazol.
abstract: OBJECTIVE
  Cerebral infarction is a major cause of death or decreasing activities of daily living. This study aimed to investigate the efficacy of commonly used antiplatelet drugs on stroke and motor and cognitive functions in relation to oxidative stress markers and insulin-like growth factor 1 receptor (IGF-1R).
  
  
  METHODS
  Stroke-prone spontaneously hypertensive rats were treated with vehicle, aspirin, clopidogrel, and cilostazol from 8 to 10 weeks of age. Physiological parameters, regional cerebral blood flow, and serum lipids were examined. Motor and cognitive functions were evaluated weekly by the Rotorod and water maze task. Spontaneous infarct volume, oxidative stress markers for lipid, protein, and DNA at the ischemic boundary zone of spontaneous infarction, and the IGF-1R-positive cell ratio in the hippocampus were immunohistochemically examined in brain sections. IGF-1Rβ expression in the hippocampus was assessed by Western blotting.
  
  
  RESULTS
  The antiplatelet drugs, cilostazol and clopidogrel, reduced the spontaneous infarct volume more than aspirin. Only cilostazol improved motor and cognitive functions with a significant increase (P<0.05) in the memory-related IGF-1R-positive ratio and IGF-1Rβ expression in the hippocampus. Cilostazol reduced the 4 oxidative stress markers in affected neurons in stroke-prone spontaneously hypertensive rats regardless of blood pressure, regional cerebral blood flow, or serum lipid levels.
  
  
  CONCLUSIONS
  The present results suggest that a possible pleiotropic effect of cilostazol resulted in the reduction of spontaneous infarct volume and preservation of motor and spatial cognitive functions. The increase of IGF-1R-positive cells in the hippocampal CA1 region could partly explain the preservation of spatial cognitive function in stroke-prone spontaneously hypertensive rats.
authors.affiliation: Department of Neurology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Omote
authors.forename: Kentaro
authors.initials: K
authors.lastname: Deguchi
authors.forename: FengFeng
authors.initials: F
authors.lastname: Tian
authors.forename: Hiromi
authors.initials: H
authors.lastname: Kawai
authors.forename: Tomoko
authors.initials: T
authors.lastname: Kurata
authors.forename: Toru
authors.initials: T
authors.lastname: Yamashita
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Ohta
authors.forename: Koji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002544:Cerebral Infarction / Q000188:drug therapy / Q000378:metabolism; D000077407:Cilostazol; D000077144:Clopidogrel; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis*; D013777:Tetrazoles / Q000494:pharmacology*; D013988:Ticlopidine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D009419:Nerve Tissue Proteins; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D000077144:Clopidogrel; D017526:Receptor, IGF Type 1; D000077407:Cilostazol; D013988:Ticlopidine; D001241:Aspirin