Pharmacological Treatment of Vascular Dementia: A Molecular Mechanism Perspective

Kuang, Huang; Zhou, Zhifeng; Zhu, Yuanchang; Wan, Zhikai; Yang, Mei-wen; Hong, Fashui; Yang, Shu‐Long

doi:10.14336/ad.2020.0427

Cited by 41 publications

(33 citation statements)

References 158 publications

(176 reference statements)

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“…Vascular dementia (VaD) is a neurodegenerative disease characterized by progressive cognitive deficits with a negative impact on patient's quality of life. It is considered the second most prevalent type of dementia worldwide, resulting in extensive medical and economic troubles in society [ 1 ].…”

Section: Introductionmentioning

confidence: 99%

Sitagliptin Attenuates the Cognitive Deficits in L-Methionine-Induced Vascular Dementia in Rats

Khodir

Faried

Abd-Elhafiz

et al. 2022

BioMed Research International

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Vascular dementia (VaD) is the second most prevalent type of dementia characterized by progressive cognitive deficits and is a major risk factor for the development of Alzheimer’s disease and other neurodegenerative disorders. This study is aimed at determining the potential neuroprotective effect of sitagliptin (STG) on cognitive deficits in L-methionine-induced VaD in rats and the possible underlying mechanisms. 30 adult male Wistar albino rats were divided equally ( n = 10 ) into three groups: control, VaD, and VaD + STG groups. The cognitive performance of the animals was conducted by open field, elevated plus maze, Y-maze, novel object recognition, and Morris water maze tests. Serum homocysteine, TNF-α, IL-6, IL-10, total cholesterol, and triglycerides levels were assessed together with hippocampal MDA, SOD, and BDNF. Histopathological and immunohistochemical assessments of the thoracic aorta and hippocampus (CA1 region) were also performed. Chronic L-methionine administration impaired memory and learning and induced anxiety. On the other hand, STG protected against cognitive deficits through improving oxidative stress biomarkers, inflammatory mediators, lipid profiles, and hippocampus level of BDNF as well as decreasing caspase-3 and GFAP and increasing Ki-67 immunoreactions in the hippocampus. Also, STG improved the endothelial dysfunction via upregulation of aortic eNOS immunoreaction. STG improved the cognitive deficits of L-methionine-induced VaD by its antioxidant, anti-inflammatory, antiapoptotic, and neurotrophic effects. These findings suggest that STG may be a promising future agent for protection against VaD.

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Section: Introductionmentioning

confidence: 99%

Sitagliptin Attenuates the Cognitive Deficits in L-Methionine-Induced Vascular Dementia in Rats

Khodir

Faried

Abd-Elhafiz

et al. 2022

BioMed Research International

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“…Given the association between increased oxidative stress during CCH and increased BBB permeability, preventing or inherently reversing BBB breakdown through antioxidant therapies may be a target for the treatment of VaD as described here 127 . Antioxidant therapy such as ocimum sanctum (OS) has been reported to reduce lipid peroxidation after CCH was induced in rats 128 .…”

Section: The Blood-brain Barrier In Health and Diseasementioning

confidence: 99%

Pathophysiology of blood brain barrier dysfunction during chronic cerebral hypoperfusion in vascular cognitive impairment

Rajeev¹,

Fann²,

Dinh³

et al. 2022

Theranostics

103

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The prevalence of cerebrovascular disease increases with age, placing the elderly at a greater lifetime risk for dementia. Vascular cognitive impairment (VCI) encompasses a spectrum of cognitive deficits from mild cognitive impairment to dementia. VCI and its most severe form, vascular dementia (VaD), is becoming a major public health concern worldwide. As growing efforts are being taken to understand VCI and VaD in animal models and humans, the pathogenesis of the disease is being actively explored. It is postulated that chronic cerebral hypoperfusion (CCH) is a major cause of VCI. CCH activates a molecular and cellular injury cascade that leads to breakdown of the blood brain barrier (BBB) and neurodegeneration. The BBB tightly regulates the movement of substances between the blood and the brain, thereby regulating the microenvironment within the brain parenchyma. Here we illustrate how BBB damage is causal in the pathogenesis of VCI through the increased activation of pathways related to excitotoxicity, oxidative stress, inflammation and matrix metalloproteinases that lead to downstream perivascular damage, leukocyte infiltration and white matter changes in the brain. Thus, CCH-induced BBB damage may initiate and contribute to a vicious cycle, resulting in progressive neuropathological changes of VCI in the brain. This review outlines the molecular and cellular mechanisms that govern BBB breakdown during CCH and highlights the clinical evidence in identifying at-risk VCI patients.

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“…The hippocampus is closely associated with learning and memory, which is particularly vulnerable to ischemic damage ( Zhu et al, 2018 ). Ischemia and hypoxia of the brain lead to the accumulation of free radicals and excitatory amino acids in blood supply area of middle cerebral artery such as the cortex, hippocampus, and striatum, which results in intracellular calcium overload and neuronal apoptosis, even necrosis ( van der Flier et al, 2018 ; Wang et al, 2020 ; Kuang et al, 2021 ). Since the GSK3β/β-catenin signaling pathway plays a critical role in neuronal cell growth, it is regarded as an important signaling pathway in the pathological mechanism of VD ( Foulquier et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Chinese Medicine, Succinum, Ameliorates Cognitive Impairment of Carotid Artery Ligation Rats and Inhibits Apoptosis of HT22 Hippocampal Cells via Regulation of the GSK3β/β-Catenin Pathway

Wei

Zhu²,

Zheng³

et al. 2022

Front. Pharmacol.

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Succinum is an organic mineral formed from the resin of ancient coniferous and leguminous plants, which is applied for tranquilizing mood, promoting blood circulation, and removing blood stasis in Chinese medicine. For quite a long time, the modern research of succinum mainly focuses on the study of physical and chemical properties and authenticity identification while few reports on its medicinal mechanism. In current study, we evaluated different solvent extracts of succinum on carotid artery ligation rats mimicking vascular dementia. It was found that ethyl acetate extracts of succinum significantly improved the learning and memory abilities of model rats and inhibited neuronal apoptosis in the hippocampus. On a mice hippocampal neuronal cell line (HT22), ethyl acetate extracts of succinum also exerted better action trend in inhibiting cell apoptosis induced by oxygen glucose deprivation (OGD). By using XAV-939 on both in vivo and in vitro studies, it was found that ethyl acetate extracts of succinum might exert these functions by regulating the GSK3β/β-catenin pathway. These studies revealed the neuronal function of succinum, which explained the traditional effects of succinum and provided more modern scientific basis for its clinical application.

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Pharmacological Treatment of Vascular Dementia: A Molecular Mechanism Perspective

Cited by 41 publications

References 158 publications

Sitagliptin Attenuates the Cognitive Deficits in L-Methionine-Induced Vascular Dementia in Rats

Sitagliptin Attenuates the Cognitive Deficits in L-Methionine-Induced Vascular Dementia in Rats

Pathophysiology of blood brain barrier dysfunction during chronic cerebral hypoperfusion in vascular cognitive impairment

Chinese Medicine, Succinum, Ameliorates Cognitive Impairment of Carotid Artery Ligation Rats and Inhibits Apoptosis of HT22 Hippocampal Cells via Regulation of the GSK3β/β-Catenin Pathway

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