Effects of the duration of hyperlipidemia on cerebral lipids, vessels and neurons in rats.
BACKGROUND
The present study was designed to investigate the effects of hyperlipidemia on the cerebral lipids, vessels and neurons of rats, and to provide experimental evidence for subsequent intervention.


METHOD
One hundred adult SD rats, half of which were male and half of which were female, were randomly divided into five groups on the basis of serum total cholesterol (TC) levels. Four groups were fed a hypercholesterolemic diet (rat chow supplemented with 4% cholesterol, 1% cholic acid and 0.5% thiouracil - this is also called a CCT diet) for periods of 1 week, 2 weeks, 3 weeks and 4 weeks, respectively. A control group was included. The levels of serum lipids, cerebral lipids, free fatty acids (FFA), interleukin-6 (IL-6), interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-α), vascular endothelial growth factor (VEGF), oxidized low density lipoprotein (ox-LDL), A-beta precursor proteins (APP), amyloid beta (Aβ), glial fibrillary acidic protein (GFAP) and tight junction protein Claudin-5 were measured after the experiment. The pathologic changes and apoptosis of the rat brains were evaluated.


RESULTS
Compared with the control group, after 1 week of a CCT diet, the levels of serum total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and brain triglycerides had increased by 2.40, 1.29 and 1.75 and 0.3 times, respectively. The serum high density lipoprotein cholesterol (HDL-C) had decreased by 0.74 times (P < 0.05) and the expression of IL-1, TNF-α and GFAP in the brains had increased (P < 0.05). In the second week, the expression of FFA and APP in the brains, and the amount of apoptotic neurons, had increased (P < 0.05). In the third week, the levels of VEGF, Ox-LDL and Aβ had increased, and the expression of Claudin-5 had decreased in the brains (P < 0.05). In the fourth week, the levels of TC, LDL-C and the amount of apoptotic neurons had increased (P < 0.05). The correlation analysis showed a positive correlation among FFA, TNF-α, VEGF, ox-LDL, Aβ, GFAP and neuronal apoptosis in the rat brains, and they all were negatively correlated with Claudin-5 (P < 0.05).


CONCLUSION
Hyperlipidemia may activate astrocytes by means of high levels of TG that will have direct toxic effects on the cerebral vessels and neurons by causing the secretion of TNF-α and IL-1 in the brains of rats. In the metabolic procession, brain tissue was shown to generate FFA that aggravated the biosynthesis of ox-LDL. With the extension of the duration of hyperlipidemia, high levels of cerebral TC and LDL-C were shown to aggravate the deposition of Aβ, induce the secretion of VEGF, reduce the expression of tight junction protein Claudin-5 and change the permeability of blood-brain barriers to factors that could damage cerebral vessels and neurons.
['Yang|Weichun|W|', 'Shi|He|H|', 'Zhang|Jianfen|J|', 'Shen|Ziyi|Z|', 'Zhou|Guangyu|G|', 'Hu|Minyu|M|']
D016564:Amyloid beta-Protein Precursor D000818:Animals D001253:Astrocytes D001808:Blood Vessels D001921:Brain D002097:C-Reactive Protein D008078:Cholesterol, LDL D062507:Claudin-5 D059305:Diet, High-Fat D005230:Fatty Acids, Nonesterified D005260:Female D005786:Gene Expression Regulation D005904:Glial Fibrillary Acidic Protein D006949:Hyperlipidemias D015850:Interleukin-6 D008077:Lipoproteins, LDL D008297:Male D009474:Neurons D051381:Rats D017207:Rats, Sprague-Dawley D015398:Signal Transduction D013997:Time Factors D014280:Triglycerides D014409:Tumor Necrosis Factor-alpha D042461:Vascular Endothelial Growth Factor A
Hyperlipidemia Cerebral lipid Neurons Cerebral vessels Duration time