title: Neurohistological and behavioral changes following the four-vessel occlusion/internal carotid artery model of chronic cerebral hypoperfusion: comparison between normotensive and spontaneously hypertensive rats.
abstract: Chronic cerebral hypoperfusion (CCH) may be a prodromal feature of aging-related dementias, and chronic hypertension is a major risk factor. We used a permanent, four-vessel occlusion/internal carotid artery (4-VO/ICA) model to evaluate the cognitive and neurohistological outcomes of CCH in both young and middle-aged rats. Young rats are asymptomatic after permanent 4-VO/ICA, and we tested the hypothesis that chronic hypertension aggravates the outcomes of CCH. Young normotensive rats (NTRs) and young spontaneously hypertensive rats (SHRs) were first subjected to 4-VO/ICA and then examined for hippocampal and cortical neurodegeneration 7, 15, and 30 days later. In a second experiment, both NTRs and SHRs were then trained in a modified, non-food-rewarded aversive radial maze (AvRM) task until acquiring asymptotic performance and then subjected to 4-VO/ICA. Thirty days later, they were assessed for memory retention of the previously acquired cognition. In a third, post hoc experiment, middle-aged NTRs were trained in the AvRM, subjected to 4-VO/ICA, and tested for memory retention 30 days later. Compared with NTRs, both SHRs and middle-aged NRTs had severe hippocampal and cortical damage, but they did not differ from each other, regardless of the chronicity of 4-VO/ICA. In contrast, NTRs were behaviorally asymptomatic, and retrograde memory performance was persistently impaired in SHRs. This amnesic effect in the SHR group was very similar to the middle-aged NTR group. These findings suggest that chronic hypertension deteriorates the capacity of the brain to adaptively respond to CCH. This influence of hypertension may parallel the effect of aging.
authors.affiliation: Department of Pharmacology and Therapeutics, State University of Maringá, Av. Colombo, 5790, Maringá, Paraná, CEP 87020-900, Brazil.
authors.forename: Cássia
authors.initials: C
authors.lastname: Valério Romanini
authors.forename: Emilene
authors.initials: E
authors.lastname: Dias Fiuza Ferreira
authors.forename: Cristiano
authors.initials: C
authors.lastname: Correia Bacarin
authors.forename: Mario Henrique
authors.initials: MH
authors.lastname: Verussa
authors.forename: Rúbia Maria
authors.initials: RM
authors.lastname: Weffort de Oliveira
authors.forename: Humberto
authors.initials: H
authors.lastname: Milani
mesh_terms: D000367:Age Factors; D000648:Amnesia, Retrograde / Q000209:etiology*; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002340:Carotid Artery Diseases / Q000150:complications* / Q000401:mortality / Q000473:pathology*; D002343:Carotid Artery, Internal / Q000473:pathology*; D002540:Cerebral Cortex / Q000473:pathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000209:etiology* / Q000473:pathology; D051381:Rats; D011918:Rats, Inbred SHR
keywords: 4-VO/ICA model; Aging; Chronic cerebral hypoperfusion; Chronic hypertension; Memory impairment; neurodegeneration