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.
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.
Barros
Carla Aparecida
CA
Department of Pharmacology, Health Science Center, State University of Maringá, Av. Colombo 5790, CEP 87020-900 Maringá, Paraná, Brazil.
Ekuni
Roberta
R
Moro
Marco Aurélio
MA
Pereira
Francine Martins
FM
Dos Santos Pereira
Marli Aparecida
MA
Milani
Humberto
H
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