title: The cognitive and histopathological effects of chronic 4-vessel occlusion in rats depend on the set of vessels occluded and the age of the animals.
abstract: Continuing previous efforts to develop the 4-vessel occlusion (4-VO) model of chronic cerebral hypoperfusion (CCH), here we evaluated whether permanent, stepwise 4-VO causes both learning deficits, hippocampal neurodegeneration and retinal lesion in young, middle-aged or aged rats. Chronic 4-VO was induced by ligation of different sets of vessels, i.e., the vertebral arteries (VA) plus common carotid arteries (CCA) (4-VO/CCA model) or the VA plus internal carotid arteries (ICA) (4-VO/ICA model) with a 1-week interstage interval. Forty days after the 4-VO, the rats were tested for spatial learning impairment, and then examined for hypoxic/ischemic damage. Young, 4-VO/CCA rats exhibited cognitive impairment, hippocampal neurodegeneration and retinal lesion (p<0.0001-0.05). After 4-VO/ICA, neither young nor middle-aged rats exhibited any learning deficits, hippocampal or retinal damage. In aged rats, chronic 4-VO/ICA caused a mild learning deficit (p<0.05). A significant effect of training was observed for the old, sham-operated rats (p<0.0001-0.001), but not for the aged 4-VO/ICA rats (p>0.05). On average, hippocampal cell density did not change after 4-VO/ICA in aged rats, but 3 of 10 subjects exhibited reduced pyramidal cell counts in all hippocampal subfields. Retinal morphology appeared to be unaffected in the 4-VO/ICA aged rats. These data suggest that the 4-VO/ICA model, but not the 4-VO/CCA model, is a suitable paradigm to study the behavioral outcome of CCH given the preservation of the retina after 4-VO/ICA. Moreover, the age at which 4-VO/ICA occurs seems to be an important factor for determining the behavioral and neuropathological changes.
authors.affiliation: Department of Pharmacology, Health Science Center, State University of Maringá, Av. Colombo 5790, CEP 87020-900 Maringá, Paraná, Brazil.
authors.forename: Carla Aparecida
authors.initials: CA
authors.lastname: Barros
authors.forename: Roberta
authors.initials: R
authors.lastname: Ekuni
authors.forename: Marco Aurélio
authors.initials: MA
authors.lastname: Moro
authors.forename: Francine Martins
authors.initials: FM
authors.lastname: Pereira
authors.forename: Marli Aparecida
authors.initials: MA
authors.lastname: Dos Santos Pereira
authors.forename: Humberto
authors.initials: H
authors.lastname: Milani
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001925:Brain Damage, Chronic / Q000473:pathology / Q000503:physiopathology*; D002545:Brain Ischemia / Q000473:pathology / Q000503:physiopathology*; D017536:Carotid Artery, Common / Q000503:physiopathology / Q000601:surgery; D002343:Carotid Artery, Internal / Q000503:physiopathology / Q000601:surgery; D002452:Cell Count / Q000379:methods; D002560:Cerebrovascular Circulation / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology; D008026:Ligation / Q000379:methods; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008568:Memory / Q000502:physiology; D017966:Pyramidal Cells / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000473:pathology; D013028:Space Perception / Q000502:physiology; D014711:Vertebral Artery / Q000503:physiopathology / Q000601:surgery