title: Cilostazol minimizes venous ischemic injury in diabetic and normal rats.
abstract: We evaluated the effects of cilostazol on venous infarction produced by a photothrombotic two-vein occlusion (2VO) model in diabetic and control rats. The cerebral blood flow (CBF) between the occluded veins was measured by laser Doppler flowmetry for 4 hours after 2VO. Infarct size and immunohistochemistry were evaluated 24, 48, 96, and 168 hours after 2VO. Cilostazol was administered 1 hour after 2VO, and thereafter at a continuous oral dose of 60 mg/kg per day. Cilostazol reduced the infarct size, and the number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)-positive apoptotic and B-cell lymphoma 2-associated X protein (Bax)-positive cells, and improved the CBF in control rats. In diabetic rats, cilostazol reduced the infarct size, and the number of TUNEL-positive apoptotic and Bax-positive cells, 96 and 168 hours after 2VO, but did not improve the CBF 4 hours after 2VO. Cilostazol increased the number of B-cell lymphoma 2 (Bcl-2)-positive cells in both strains 48, 96, and 168 hours after 2VO, but did not improve vessel wall thickness or collagen deposits. Cilostazol appeared to limit venous infarcts by improving the penumbral CBF in nondiabetic rats, and inhibited pro-apoptotic changes through Bcl-2 overexpression, without improving the CBF in diabetic rats.
authors.affiliation: Department of Neurosurgery, Nara Medical University School of Medicine, Nara, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Wajima
authors.forename: Mitsutoshi
authors.initials: M
authors.lastname: Nakamura
authors.forename: Kaoru
authors.initials: K
authors.lastname: Horiuchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeshima
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Nishimura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakase
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020520:Brain Infarction / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D000077407:Cilostazol; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D007150:Immunohistochemistry; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D013777:Tetrazoles / Q000494:pharmacology*; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D005343:Fibrinolytic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D013777:Tetrazoles; D051028:bcl-2-Associated X Protein; D000077407:Cilostazol