RESUMO
INTRODUCTION: Chronic hypoperfusion in rats produces memory and learning impairments due to permanent occlusion of commun carotid arteries (POCCA). Molecular mechanisms leading to behavioural disorders have been poorly studied. For this reason, the aim of the present study was to characterise oxidative metabolism disorders and their implications in memory and learning impairments. METHODS: Superoxide dismutase (SOD) and catalase (CAT) activities were determined in cortex, hippocampus and striatum homogenates at 24 hours and at 22 days after the lesion. Haematoxylin-eosin staining and glial fibrillary acidic protein (GFAP) immunoreactivity were performed on coronal sections. Behavioural impairments were explored using the Morris water maze (MWM). Escape latencies were determined in all behavioural studies. RESULTS: The lesion induced a significant increase (P<.01) in CAT activity in the cortex at 24 hours, while SOD activity was significantly higher (P<.01) in the cortex and hippocampus at 22 days. An intense vacuolization was observed in the cortex and striatum as a result of the lesion. A neuronal loss in the striatum and hippocampus was observed. The glial reaction increased in the cortex and striatum. Visual alterations were observed in the lesion group with the lowest evolution time (P<.001). Escape latencies, corresponding to MWM schemes for long-term and short-term memory evaluation increased significantly (P<.05) in both groups of lesioned animals. CONCLUSION: It was concluded that changes in SOD and CAT activities indicate a possible implication of oxidative imbalance in the pathology associated with chronic cerebral hypoperfusion. In addition, the POCCA model in rats is useful for understanding mechanisms by which cerebral hypoperfusion produces memory and learning impairments.
Assuntos
Isquemia Encefálica/metabolismo , Isquemia Encefálica/psicologia , Aprendizagem/fisiologia , Memória/fisiologia , Animais , Artéria Carótida Primitiva/patologia , Estenose das Carótidas/metabolismo , Estenose das Carótidas/psicologia , Masculino , Aprendizagem em Labirinto/fisiologia , Motivação/fisiologia , Proteínas do Tecido Nervoso/efeitos dos fármacos , Oxirredução , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/metabolismoRESUMO
The animal model of aged monkeys is a good homologue of Alzheimer's disease in humans, in which it has been shown that there is disproportionate slowing of the EEG when compared with healthy subjects paired for age. This is found both on the conventional EEG and quantitatively. In the latter, relative energy has been the measurement most commonly used for diagnosis and follow-up with various treatments. The follow-up parameters evaluated in this study were: absolute and relative energy of the quantitative EEG (EEGq) obtained in an aged (39 year old) baboon (Papio hamadryas) before and after infusion of intraventricular nerve growth factor (NGF). These findings were compared with those of a young animal (6 year old) of the same species, treated in the same way. Since the animals were first anaesthetized with ketamine and diacepam so as to be able to carry out the study, we used a cerebral function analyzer which allowed us to ascertain that the changes found on analysis of the EEGq were not due to the depth of anaesthesia. The analyzer evaluated the tendencies of amplitude and frequency of the EEG, which is a method widely used for the indirect evaluation of the level of anaesthesia.
Assuntos
Envelhecimento , Encéfalo/patologia , Encéfalo/fisiologia , Ventrículos Cerebrais/efeitos dos fármacos , Eletroencefalografia , Fatores de Crescimento Neural/farmacologia , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/patologia , Animais , Mapeamento Encefálico , Seguimentos , Injeções Intraventriculares , Fatores de Crescimento Neural/administração & dosagem , PapioRESUMO
El modelo animal de monos envejecidos constituye un buen homológo de la enfermedad de Alzheimer en humanos, en la cual se ha constatado un enlentecimiento desproporcional del EEG cuando se compara con sujetos sanos pareados en edad, hallazgo evidenciado tanto en el EEG convencional como en el cuantitativo; en este último la energía relativa ha sido la medida más comúnmente utilizada para el diagnóstico y seguimiento evolutivo con diversas terapéuticas. En el presente estudio se evalúan los parámetros: energía absoluta y relativa del EEG cuantitativo (EEGq) obtenido en un babuino (Papio hamadryas) envejecido (39 años) en los períodos pre y postinfusion intraventricular de factor de crecimiento de nervio (FCN) y se compara con un animal joven (6 años) de la misma especie sometido a idéntica terapia. Dado que para la realización de este estudio los animales fueron previamente anestesiados con ketamina y diacepam, empleamos un analizador de la función cerebral que nos permitió comprobar que los cambios reportados en el análisis del EEGq no respondían a la profundidad de la anestesia. Este analizador evalúa las tendencias de amplitud y frecuencia del EEG el cual ha sido un método frecuentemente utilizado en la evaluación indirecta del nivel de anestesia