title: Enhanced cerebral ischemic lesions after two-vein occlusion in diabetic rats.
abstract: The two-vein occlusion (2VO) model is known to be useful for ischemic penumbra studies in vivo. It was applied here to examine sequential changes of regional cerebral blood flow (CBF) and cerebral venous infarction in normal (Long-Evans Tokushima Otsuka, LETO) and diabetic (Otsuka Long-Evans Tokushima Fatty, OLETF) rats. The aim of our study was to examine and compare the ischemic pathogenesis related to regional changes in cerebral blood flow (CBF) induced with 2VO in diabetic OLETF and non-diabetic LETO rats. Two cortical veins were occluded photochemically by using rose bengal dye in 10 OLETF and 10 LETO rats. All animals were killed with perfusion fixation at 48 h after 2VO. Bax and Bcl-2 staining was performed along with the terminal deoxynucleotidyl transderase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) assay to examine the relationship to single-cell death. Smooth muscle actin and Van Gieson's elastic staining were done for assessment of thickening of the vessel walls. Not only the volume of cerebral cortex affected by 2VO-induced venous infarction was increased in diabetic OLETF rats, but we also observed significantly reduced CBF at 90 min after 2VO, coupled with increased apoptosis in and around ischemic lesions. Morphologically, OLETF rats demonstrated marked thickening of the walls in the small cerebral vessels with perivascular fibrosis, indicating more severe cerebral microvascular atherosclerotic changes as compared to their non-diabetic LETO counterparts. The OLETF rat thus appears to be an excellent animal model for studying the diabetic enhancement of venous ischemia induced by 2VO.
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: Hitoshi
authors.initials: H
authors.lastname: Miyake
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeshima
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tamura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Motoyama
authors.forename: Noboru
authors.initials: N
authors.lastname: Konishi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nakase
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001160:Arterioles / Q000473:pathology / Q000503:physiopathology; D020520:Brain Infarction / Q000473:pathology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D016923:Cell Death / Q000502:physiology; D002550:Cerebral Veins / Q000473:pathology / Q000503:physiopathology* / Q000601:surgery; D002560:Cerebrovascular Circulation / Q000235:genetics*; D048909:Diabetes Complications / Q000473:pathology / Q000503:physiopathology*; D004195:Disease Models, Animal; D005355:Fibrosis / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D020287:In Situ Nick-End Labeling; D010775:Photic Stimulation / Q000379:methods; D010777:Photochemistry; D051381:Rats; D020334:Rats, Inbred OLETF; D012395:Rose Bengal; D020246:Venous Thrombosis / Q000473:pathology / Q000503:physiopathology*; D014699:Venules / Q000473:pathology / Q000503:physiopathology
chemical_list: D051017:Apoptosis Regulatory Proteins; D012395:Rose Bengal