title: Cilostazol protects against microvascular brain injury in a rat model of type 2 diabetes.
abstract: Cilostazol, a pluripotent phosphodiesterase III-specific inhibitor with anti-platelet and vasculogenic effects, is useful for preventing recurrent brain vascular events, particularly in stroke patients with diabetes mellitus (DM). However, it is unclear whether cilostazol affects autoregulatory responses in small cerebral arteries. Thus, we investigated the effect of cilostazol on diabetic brain vasculopathy in a model of type II DM using male OLETF rats. OLETF rats were treated with either cilostazol (CG) or vehicle (VG) and subjected to microangiography with monochromatic synchrotron radiation to investigate middle cerebral artery (MCA) vasoreactivity following an injection of acetylcholine (Ach). Ach administration led to MCA diameter contraction in the VG, but MCA dilation in the CG. We also evaluated morphological changes in the small intracranial vessels and found that in the CG, the endothelial cell structure in the small artery was not destroyed. Moreover, protein levels of phosphorylated endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) were higher in each evaluated brain region in CG rats vs. VG rats. Our results suggest that cilostazol could potentially improve autoregulatory responses in the small cerebral arteries by increasing eNOS phosphorylation and VEGF expression in DM, and thus, may act as a neurovascular protectant.
authors.affiliation: Department of Neurology, Tokai University School of Medicine, 143 Shimo-Kasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Tsukamoto
authors.affiliation: Department of Neurology, Tokai University School of Medicine, 143 Shimo-Kasuya, Isehara, Kanagawa, 259-1193, Japan. Electronic address: enagata@is.icc.u-tokai.ac.jp.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Nagata
authors.affiliation: Department of Physiology, Tokai University School of Medicine, 143 Shimo-Kasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Fukuyama
authors.affiliation: Support Center for Medical Research and Education, Tokai University, 143 Shimo-Kasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Department of Neurology, Tokai University School of Medicine, 143 Shimo-Kasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yuzawa
authors.affiliation: Department of Neurology, Tokai University School of Medicine, 143 Shimo-Kasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Saori
authors.initials: S
authors.lastname: Kohara
authors.affiliation: Department of Neurology, Tokai University School of Medicine, 143 Shimo-Kasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Mie
authors.initials: M
authors.lastname: Shimizu
authors.affiliation: Support Center for Medical Research and Education, Tokai University, 143 Shimo-Kasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Takahari
authors.affiliation: Department of Neurology, Tokai University School of Medicine, 143 Shimo-Kasuya, Isehara, Kanagawa, 259-1193, Japan.
authors.forename: Shunya
authors.initials: S
authors.lastname: Takizawa
mesh_terms: D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D000077407:Cilostazol; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects*; D008297:Male; D055806:Microvessels / Q000187:drug effects*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D051381:Rats; D020334:Rats, Inbred OLETF; D013777:Tetrazoles / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D013777:Tetrazoles; D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000077407:Cilostazol
keywords: Cilostazol; Diabetes mellitus; Endothelial cell function; Microangiography