Abstract
Chronic cerebral hypoperfusion (CCH) is a main cause of vascular dementia and is also an etiological factor of neurological diseases and mental disorders. However, few treatments are available for CCH, and new medications are needed. In the present study, we employed a rat model of CCH that was based on bilateral common carotid artery occlusion and investigated the therapeutic effects of resveratrol and its detailed mechanism of action. We evaluated neurological deficit scores and performed the Morris water maze test, hematoxylin and eosin staining, TUNEL staining, enzyme-linked immunosorbent assays, and Western blot. Resveratrol reduced neurological deficit scores in CCH rats and reduced pathological damage in the frontal cortex and hippocampus. Resveratrol activated autophagy and inhibited the expression of AKT/mechanistic target of rapamycin (mTOR) signaling pathway-related proteins. Treatment with a phosphoinositide-3 kinase inhibitor reversed the protective effect of resveratrol. These findings suggest that resveratrol improves cognitive function in a rat model of CCH and reduces oxidative stress-induced neuronal damage in the frontal cortex and hippocampus by activating autophagy and inhibiting neuronal apoptosis. These effects may be regulated by the AKT/mTOR signaling pathway.
Highlights
Chronic cerebral hypoperfusion (CCH) can contribute to the development of various neurological diseases and mental disorders, including vascular dementia, Alzheimer’s disease, and Binswanger disease (Duncombe et al, 2017; Feng et al, 2018)
Neurological deficit scores increased after bilateral common carotid artery occlusion (BCCAO), and both spatial cognitive ability and spatial memory decreased in CCH rats compared with the Sham group (p < 0.05)
The retinal cortex and hippocampal CA1 area were monitored in CCH rats that were treated with resveratrol (Res group) at 3, 6, and 9 weeks of ischemia
Summary
Chronic cerebral hypoperfusion (CCH) can contribute to the development of various neurological diseases and mental disorders, including vascular dementia, Alzheimer’s disease, and Binswanger disease (Duncombe et al, 2017; Feng et al, 2018). Stage CCH is mainly characterized by cognitive impairment that is followed by biological changes, such as energy metabolism disorders, abnormal neuronal electrical activity, oxidative stress, glial cell activation, and inflammatory factor release These changes can lead to abnormal brain structure and function, including neuronal damage and degeneration of the frontal cortex and hippocampus, resulting in cognitive. We hypothesized that resveratrol would ameliorate cognitive dysfunction that is caused by chronic cerebral ischemia, likely by the activation of autophagy through the AKT/mTOR signaling pathway. To test this hypothesis, we established a rat model of CCH that was induced by bilateral common carotid artery occlusion (BCCAO). We investigated the possible involvement of the ATK/mTOR signaling pathway in the mechanism of action of resveratrol
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