A Hyperlipidemic Diet Induces Structural Changes in Cerebral Blood Vessels

Elena      Constantinescu; Florentina      Safciuc; Anca      V. Sima

Abstract

The cerebrovascular pathology is an important contributor to the death rate presently. Hyperlipidemia, an established risk factor for cardiovascular diseases, is also incriminated in the neurodegenerative disorders. The aim of this study was to evaluate the effect of a hyperlipidemic (HL) diet on the morphology of the cerebral vessels and on the amyloid deposition in the HL hamster, an accepted model of atherosclerosis. Hamsters fed a HL diet were tested periodically for serum parameters and sacrificed after 3 and 6 months. The methods used were: paraffin embedding, thioflavin S amyloid staining, fluorescence and electron microscopy (EM). Increased serum cholesterol and triglycerides characterized the HL hamsters. The carotid arteries developed fatty streaks after 3 months and atherosclerotic plaques after 6 months HL diet. The brain cortex comprised irregularly shaped microvessels with large perivascular spaces, enlarged endothelial cells (EC) and occasionally a lumen full of lipoprotein particles. The thioflavin S reaction revealed a discreet staining of the capillaries walls; the EC cytoplasm and basal lamina contained a fibrillar material, with a pattern similar to an incipient amyloid deposit. Some large meningeal vessels from animals with serum cholesterol over 1000mg/dl presented an intense autofluorescence in the adventitia; EM examination identified lipid-loaded perivascular cells in these areas. In conclusion, the detected morphological changes induced by the HL diet could represent a serious impairment for the normal brain function. These data may contribute to the better understanding of the risks of hyperlipidemia for the mental health, and its reversal could become a new therapeutic approach for neurodegenerative disorders.

Keywords: Amyloid, cerebral vessels, electron microscopy, hamster, histochemistry, hyperlipidemia, neurodegeneration, cerebrovascular, perivascular cells, meningeal, autofluorescence, fibrillar, thioflavin, endothelial cells, neurodegenerative, lipid