title: Middle-aged, but not young, rats develop cognitive impairment and cortical neurodegeneration following the four-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion.
abstract: Permanent, stepwise occlusion of the vertebral arteries (VAs) and internal carotid arteries (ICAs) following the sequence VA→ICA→ICA, with an interstage interval (ISI, →) of 7 days, has been investigated as a four-vessel occlusion (4-VO)/ICA model of chronic cerebral hypoperfusion. This model has the advantage of not causing retinal damage. In young rats, however, 4-VO/ICA with an ISI of 7 days fails to cause behavioral sequelae. We hypothesized that such a long ISI would allow the brain to efficiently compensate for cerebral hypoperfusion, preventing the occurrence of cognitive impairment and neurodegeneration. The present study evaluated whether brain neurodegeneration and learning/memory deficits can be expressed by reducing the length of the ISI and whether aging influences the outcome. Young, male Wistar rats were subjected to 4-VO/ICA with different ISIs (5, 4, 3 or 2 days). An ISI of 4 days was used in middle-aged rats. Ninety days after 4-VO/ICA, the rats were tested for learning/memory impairment in a modified radial maze and then examined for neurodegeneration of the hippocampus and cerebral cortex. Regardless of the ISI, young rats were not cognitively impaired, although hippocampal damage was evident. Learning/memory deficits and hippocampal and cortical neurodegeneration occurred in middle-aged rats. The data indicate that 4-VO/ICA has no impact on the capacity of young rats to learn the radial maze task, despite 51% hippocampal cell death. Such resistance is lost in middle-aged animals, for which the most extensive neurodegeneration observed in both the hippocampus and cerebral cortex may be responsible.
authors: Department of Pharmacology and Therapeutic, Health Science Center, State University of Maringá, Av. Colombo 5790, Maringá, Paraná, Brazil.
authors: Emilene D Fiuza
authors: ED
authors: Ferreira
authors: Cássia V
authors: CV
authors: Romanini
authors: Marco A
authors: MA
authors: Mori
authors: Rúbia M Weffort
authors: RM
authors: de Oliveira
authors: Humberto
authors: H
authors: Milani
mesh_terms: D000367:Age Factors; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology; D016923:Cell Death; D002540:Cerebral Cortex / Q000473:pathology*; D003072:Cognition Disorders / Q000209:etiology* / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000473:pathology; D009410:Nerve Degeneration / Q000209:etiology* / Q000473:pathology; D009474:Neurons / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar