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Cilostazol Minimizes Venous Ischemic Injury in Diabetic and Normal Rats
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Journal Article
Cilostazol Minimizes Venous Ischemic Injury in Diabetic and Normal Rats
2011
Overview
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.
Publisher
SAGE Publications,Nature Publishing Group,Sage Publications Ltd
Subject
/ bcl-2-Associated X Protein - metabolism
/ Biological and medical sciences
/ Brain Infarction - drug therapy
/ Brain Infarction - metabolism
/ Brain Infarction - pathology
/ Brain Infarction - physiopathology
/ Cerebrovascular Circulation - drug effects
/ Diabetes Mellitus - drug therapy
/ Diabetes Mellitus - metabolism
/ Diabetes Mellitus - pathology
/ Diabetes Mellitus - physiopathology
/ Fibrinolytic Agents - pharmacology
/ Male
/ Original
/ Pharmacology. Drug treatments
/ Proto-Oncogene Proteins c-bcl-2 - metabolism
/ Rats
/ Vascular diseases and vascular malformations of the nervous system
