title: Time-course of neurodegeneration and memory impairment following the 4-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion in middle-aged rats.
abstract: The present work extends previous studies with the aim of developing the 4-vessel occlusion/internal carotid artery (4-VO/ICA) model of chronic cerebral hypoperfusion. The permanent occlusion of the vertebral arteries (VAs) and internal carotid arteries (ICAs) followed the sequence VA→ICA→ICA. The interstage interval (ISI, →), chronicity of 4-VO/ICA, and age of the animals may determine the success of the model with regard to neurohistological and behavioral outcomes. Using middle-aged rats, the present study evaluated (i) how brain damage evolves as the ISI is reduced and duration (i.e., "chronicity") of 4-VO/ICA is prolonged and (ii) how the duration of 4-VO/ICA affects retrograde memory performance. Male Wistar rats (12-15 months of age) were subjected to 4-VO/ICA with an ISI of 7, 5, 4, or 3 days, and hippocampal and cortical damage was examined 7, 30, and 90 days later. Using an ISI of 4 days, retrograde memory performance was assessed in the aversive radial maze after 4-VO/ICA with a duration of 7, 30, and 90 days. The severity of brain neurodegeneration and rate of mortality progressively increased as the ISI length decreased from 7 to 3 days, an effect that was not significantly altered by the chronicity of 4-VO/ICA. Permanent 4-VO/ICA effectively caused retrograde amnesia, an effect that worsened as the chronicity of 4-VO/ICA was prolonged. The findings confirm and expand the notion that permanent, 3-stage 4-VO/ICA effectively produces extensive neurodegeneration and persistent learning/memory impairment in middle-aged rats and that the ISI length, more than the chronicity of 4-VO/ICA, determines the final results.
authors.affiliation: Department of Biological Sciences, Assis Gurgacz Faculty, Av. das Torres, 500, CEP 85806-095 Cascavel, Paraná, Brazil.
authors.forename: Francine Martins
authors.initials: FM
authors.lastname: Pereira
authors.forename: Emilene Dias Fiuza
authors.initials: ED
authors.lastname: Ferreira
authors.forename: Rúbia Maria Weffort
authors.initials: RM
authors.lastname: de Oliveira
authors.forename: Humberto
authors.initials: H
authors.lastname: Milani
mesh_terms: D000367:Age Factors; D000648:Amnesia, Retrograde / Q000150:complications / Q000473:pathology* / Q000523:psychology; D000818:Animals; D002340:Carotid Artery Diseases / Q000150:complications / Q000401:mortality / Q000473:pathology* / Q000523:psychology*; D002343:Carotid Artery, Internal / Q000473:pathology*; D002540:Cerebral Cortex / Q000098:blood supply / Q000473:pathology; D004195:Disease Models, Animal; D006624:Hippocampus / Q000098:blood supply / Q000473:pathology; D008297:Male; D018782:Maze Learning; D009410:Nerve Degeneration / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014711:Vertebral Artery / Q000473:pathology*