Abstract
In this paper, a curcumin derivative Cur20 was synthesized for better hydrolytic stability, which showed a higher angiogenic effect on zebrafish model than curcumin. In order to reveal the potential effects on neuroprotection, a mouse model of vascular dementia (VaD) induced by permanent right common carotid artery occlusion (rUCCAO) was established. After two weeks of curcumin administration, the cognitive function of mice was detected by Morris water maze and Y maze. The alteration on oxidative injuries and morphological damage were also analyzed by reactive oxygen species, superoxide dismutase, GSH, malondialdehyde tests, and Nissl stain on cortex/hippocampus. The angiogenesis and related signal factors were evaluated as well. The results showed that Cur20 significantly attenuated the cognitive dysfunction and histopathological changes of the VaD mice with enhanced antioxidant system and angiogenesis. In addition, primary rat brain microvessel endothelial cells (rBMECs) with oxygen glucose deprivation (OGD) were applied to further verify the possible mechanisms of Cur20-induced angiogenesis. The results demonstrated that the proliferation effect and the activation of pro-angiogenesis factors such as HIF-1α, VEGF, and TFEB might contribute to the protection of ischemic injury. Based on the above, our conclusion is that Cur20 can be considered as a promising therapeutic strategy for VaD.
Highlights
With the aging of the population and the change of dietary structure, the incidence of cardiovascular and cerebrovascular diseases increases year by year, leading to a gradual increase of dementia patients
A 30% drop in the regional cerebral blood flow was considered as a successful vascular dementia (VaD) mouse model, which was measured by laser-Doppler fluxmetry (LDF) (MP150 starter system, BIOPAC system, Inc., United States)
The mice were randomly divided into four groups: sham control group (n 6); VaD model group (n 6), which was subjected to rUCCAO; curcumin group (n 6), which was subjected to rUCCAO and treated with 20 μmol/kg curcumin; and Cur20 group (n 6), which was subjected to rUCCAO and treated with 20 μmol/kg Cur20
Summary
With the aging of the population and the change of dietary structure, the incidence of cardiovascular and cerebrovascular diseases increases year by year, leading to a gradual increase of dementia patients. Dementia is a syndrome of developmental disability that involves varying degrees of cognitive, emotional, language and consciousness disorders. Extensive clinical evidence suggests that chronic cerebral perfusion is associated with cognitive decline and hippocampal neuron damage in neurodegenerative diseases (Sinha et al, 2020). VaD, which is usually caused by multiple strokes or long-term chronic cerebral ischemia, accompanied by a gradual decline in memory, emotion control and cognitive function. It seriously damages the health of patients, affects the quality of life of patients, and imposes a heavy burden on society and families.
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