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Influence of Hypertension with Multiple Risk Factors on Brain Tissue Pathomorphology and Cognitive Impairment-Related Biomarkers
Su-rui Chang1,2, Zhen Zhang1,2, Jian-Gang Liu*1,4, Hao Li*1,3,5
1Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China, 100091
2Graduate School, China Academy of Chinese Medical Sciences, Beijing, China, 100091
3Institute of Geriatrics of China Academy of Chinese Medical Sciences, Beijing, China, 100700
4Institute of cardiovascular disease of China Academy of Chinese Medical Science, Beijing, China, 100091
5Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing, China, 100102
Abstract
Background: Hypertension is the most common chronic disease in the elderly. In China, according to a survey conducted in 2012–2015, the prevalence rate of hypertension in people aged ≥60 years was 53.24%, and for people aged ≥80 was 60.27%. Not only is hypertension the primary cause of stroke in China, it is also a risk factor for cognitive impairment diseases such as vascular dementia and Alzheimer's disease (AD). Compared with healthy people, patients with hypertension have a 1.4-fold increased risk of developing dementia. Therefore, it is important to study the characteristics of hypertension models to reveal the potential and changeable etiologies and risk factors and to slow the progress of cognitive impairment through systemic intervention, especially for vascular cognitive impairment, and prevent AD. Hyperlipidemia, diabetes mellitus, and a high-salt diet are risk factors for hypertension and cognitive impairment. It is essential to explore how these diseases injure cognitive function by assessing the pathological changes and biomarkers.
Purpose: Using a spontaneously hypertensive rat (SHR) model of metabolic syndrome (hyperlipidemia, diabetes mellitus, salt-sensitive) by feeding SHRs complex model diets (high-fat diet, high-glucose diet, and salt-sensitive diet), we assessed changes in brain tissue pathomorphology and cognitive impairment-related biomarkers.
Materials and Methods: Thirty-two male SHR were randomly divided into four groups (n=8 rats per group): SHR group (fed routine diet), HFD–SHR group (fed high-fat diet), HSD–SHR group (fed high-salt diet), and the DM -SHR group (fed high-fat, high-glucose mixed diet and injected with streptozotocin, 25 mg/kg). Eight male Wistar–Kyoto (WKY) rats (that share the same genetic background with SHR) comprised the blank control group. After 24 weeks, blood plasma was collected by the abdominal aortic method, and the plasma levels of interleukin (IL)-6, IL-1β, and hypersensitive C-reactive protein were assessed. Cortex and hippocampal homogenate was used to determine levels of inflammatory factors, acetyl cholinesterase, acetylcholine, and β-amyloid protein (β-AP). Meanwhile, pathological changes in the CA1 area of the hippocampus and the cortical histopathological structure were observed under light microscopy following hematoxylin and eosin staining, Nissl’s staining, and Golgi-Cox staining.
Results: Compared with WKY controls, the level of inflammatory and cholinergic factors in the blood and brain tissue of the four model groups decreased significantly (P<0.05), whereas the amount of β-AP increased (P<0.05). Changes in the 3‘H’ model group were more obvious; however, there was no significant difference among the model groups. Compared with WKY group, other groups were obseved the decrease in the number of neurons, space broadening, a disorganized structure, and pyknosis and condensed nuclei by HE staining. Decreasing in the number of Nissl bodies in the CA1 area were observed by Nissl’s staining.
Conclusion: Hypertension combined with lipid metabolism disorders, diabetes, or a high-salt diet can result in pathological changes to the brain tissue and influence the levels of cognitive impairment-related biomarkers. This study presents interactions between multiple risk factors and the increase in the degree of vascular dementia. And it is of great significance for identifying biomarkers to aid in the early intervention or delaying the progress of cognitive deficits caused by hypertension.
