Synergistic memory impairment through the interaction of chronic cerebral hypoperfusion and amlyloid toxicity in a rat model.
Stroke
; 42(9): 2595-604, 2011 Sep.
Article
em En
| MEDLINE
| ID: mdl-21737797
ABSTRACT
BACKGROUND AND PURPOSE:
Vascular pathology and Alzheimer disease (AD) pathology have been shown to coexist in the brains of dementia patients. We investigated how cognitive impairment could be exacerbated in a rat model of combined injury through the interaction of chronic cerebral hypoperfusion and amyloid beta (Aß) toxicity.METHODS:
In Wistar rats, chronic cerebral hypoperfusion was modeled by permanent occlusion of bilateral common carotid arteries (BCCAo). Further, AD pathology was modeled by bilateral intracerebroventricular Aß (Aß toxicity) using a nonphysiological Aß peptide (Aß 25 to 35). The experimental animals were divided into 4 groups, including sham, single injury (Aß toxicity or BCCAo), and combined injury (BCCAo-Aß toxicity) groups (n=7 per group) . Cerebral blood flow and metabolism were measured using small animal positron emission tomography. A Morris water maze task, novel object location and recognition tests, and histological investigation, including neuronal cell death, apoptosis, neuroinflammation, and AD-related pathology, were performed.RESULTS:
Spatial memory impairment was synergistically exacerbated in the BCCAo-Aß toxicity group as compared to the BCCAo or Aß toxicity groups (P<0.05). Compared to the sham group, neuroinflammation with microglial or astroglial activation was increased both in multiple white matter lesions and the hippocampus in other experimental groups. AD-related pathology was enhanced in the BCCAo-Aß toxicity group compared to the Aß toxicity group.CONCLUSIONS:
Our experimental results support a clinical hypothesis of the deleterious interaction between chronic cerebral hypoperfusion and Aß toxicity. Chronic cerebral hypoperfusion-induced perturbation in the equilibrium of AD-related pathology may exacerbate cognitive impairment in a rat model of combined injury.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Demência Vascular
/
Circulação Cerebrovascular
/
Peptídeos beta-Amiloides
/
Apoptose
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Aprendizagem em Labirinto
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Doença de Alzheimer
/
Transtornos da Memória
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
Idioma:
En
Revista:
Stroke
Ano de publicação:
2011
Tipo de documento:
Article