stilbenes and Dementia--Vascular

Pterostilbene, a methylated stilbene derived from many plant foods, has significant anti-inflammatory activity. Meanwhile, vascular dementia (VaD) is the second most common subtype of dementia, in which inflammation is one of the major pathogenic contributors. However, the protective effect of pterostilbene on VaD is not well understood. In this work, we investigated the effect of pterostilbene on VaD and explored its underlying mechanisms using in vivo and in vitro models. Y-maze and Morris water maze tests showed pterostilbene-attenuated cognitive impairment in mice with bilateral common carotid artery occlusion (BCCAO). The hippocampal neuronal death and microglial activation in BCCAO mice were also reduced by pterostilbene treatment. Further, pterostilbene inhibited the expression of TLR4 and downstream inflammatory cytokines in these mice, with similar results observed in an oxygen-glucose deprivation and reperfusion (OGD/R) BV-2 cell model. In addition, its anti-inflammatory effect on OGD/R BV-2 cells was partially blocked by TLR4 overexpression. Moreover, Triad3A-TLR4 interactions were increased by pterostilbene following enhanced ubiquitination and degradation of TLR4, and the inhibitory effect of pterostilbene on inflammation was blocked by Triad3A knockdown in OGD/R-stimulated BV-2 cells. Together, these results reveal that pterostilbene could reduce vascular cognitive impairment and that Triad3A-mediated TLR4 degradation might be the key target.

Topics: Animals; Anti-Inflammatory Agents; Dementia, Vascular; Glucose; Mice; Microglia; Stilbenes; Toll-Like Receptor 4; Ubiquitination

We aimed to quantitatively and qualitatively assess whether there is a discrepancy in detecting amyloid beta (Aβ) positivity between 18F-florbetaben (FBB) and 18F-flutemetamol (FMM) positron emission tomography (PET). We obtained paired FBB and FMM PET images from 107 participants. Three experts visually quantified the Aβ deposition as positive or negative. Quantitative assessment was performed using global cortical standardized uptake value ratio (SUVR) with the whole cerebellum as the reference region. Inter-rater agreement was excellent for FBB and FMM. The concordance rates between FBB and FMM were 94.4% (101/107) for visual assessment and 98.1% (105/107) for SUVR cut-off categorization. Both FBB and FMM showed high agreement rates between visual assessment and SUVR positive or negative categorization (93.5% in FBB and 91.2% in FMM). When the two ligands were compared based on SUVR cut-off categorization as standard of truth, although not statistically significant, the false-positive rate was higher in FMM (9.1%) than in FBB (1.8%) (p = 0.13). Our findings suggested that both FBB and FMM had excellent agreement when used to quantitatively and qualitatively evaluate Aβ deposits, thus, combining amyloid PET data associated with the use of different ligands from multi-centers is feasible.

Topics: Aged; Aged, 80 and over; Alzheimer Disease; Amyloid beta-Peptides; Aniline Compounds; Benzothiazoles; Case-Control Studies; Cognitive Dysfunction; Dementia, Vascular; False Negative Reactions; False Positive Reactions; Female; Fluorine Radioisotopes; Humans; Male; Middle Aged; Plaque, Amyloid; Positron-Emission Tomography; Radiopharmaceuticals; Stilbenes

This study was intended to investigate whether treatment with resveratrol and melatonin alone or in combination can exert neurorestorative effects in a rat model of vascular dementia.. Briefly, male Wistar rats were subjected to permanent bilateral common carotid artery occlusion (BCCAO) by surgery. After 4 weeks, the cognitive deficits were assessed using the Morris water maze and novel object recognition tests. The biochemical parameters of oxidative stress and inflammation were also assessed.. Rats in the BCCAO group showed cognitive deficits, accompanied by oxidonitrosative stress, neuroinflammation, and a reduction in brain-derived neurotrophic factor (BDNF) in the hippocampus region. Moreover, the acetylcholinesterase activity in the hippocampus was found to be increased in the BCCAO group compared to the sham group. The 4-week treatment with melatonin (10 mg/kg) and resveratrol (20 mg/kg) alone and in combination (melatonin 5 mg/kg and reseveratrol 10 mg/kg) caused a significant improvement in the cognitive deficits induced by BCCAO, accompanied by a reversal of oxidonitrosative stress, neuroinflammation, and BDNF depletion in the hippocampus region. Additionally, the treatment with melatonin and resveratrol significantly decreased acetylcholinesterase activity compared to in the BCCAO group. Melatonin and resveratrol ameliorated the BDNF expression of hippocampal protein.. These results emphasize that coadministration of melatonin and resveratrol can be beneficial in BCCAO-induced vascular dementia through changes in BDNF expressions.

Topics: Animals; Antioxidants; Brain-Derived Neurotrophic Factor; Dementia, Vascular; Disease Models, Animal; Drug Therapy, Combination; Glutathione; Hippocampus; Interleukin-1beta; Male; Malondialdehyde; Maze Learning; Melatonin; Memory Disorders; Models, Molecular; Rats; Rats, Wistar; Recognition, Psychology; Resveratrol; Stilbenes; Tumor Necrosis Factor-alpha

Resveratrol appears to have neuroprotective potential in various animal models of brain disorders including cerebral ischemia and neurodegenerative diseases. Chronic cerebral hypoperfusion is a well-known pathological condition contributing to the neurodegenerative diseases such as vascular dementia. Purpose of the present study is to evaluate the possible therapeutic potential of resveratrol in a model of vascular dementia of ovariectomized female rats. Assessment of the potential was based on the determination of brain oxidative status, caspase-3 level, glial fibrillary acidic protein (GFAP), and neuronal damage on hippocampus and cerebral cortex.. For creating the model of chronic cerebral hypoperfusion, ovariectomized female Wistar rats were subjected to the modified two vessel occlusion method, with the right common carotid artery being occluded first and the left one a week later.. At the 15th day following the ligation, neuronal damage was accompanied by the increased immunoreactivities of both GFAP and caspase-3, and significant neurodegeneration was evident in the hippocampus and cortex, all of which were significantly alleviated with resveratrol treatment (10 mg/kg). Biochemical analysis revealed that the resveratrol treatment decreased lipid peroxidation and restored reduced glutathione level as well.. The collected data of the present study suggest that the administration of resveratrol may provide a remarkable therapeutic benefit for vascular dementia, which is most likely related to the prevention of both apoptotic cell death and oxidative stress. We believe that therapeutic efficacy of resveratrol deserves to be tested for potential clinical application in postmenopausal elderly women suffering from vascular dementia.

Topics: Animals; Antioxidants; Apoptosis; Biomarkers; Caspase 3; Cerebral Cortex; Dementia, Vascular; Dietary Supplements; Disease Models, Animal; Female; Glial Fibrillary Acidic Protein; Glutathione; Hippocampus; Lipid Peroxidation; Neuroprotective Agents; Ovariectomy; Oxidative Stress; Random Allocation; Rats, Wistar; Resveratrol; Stilbenes

Dementia is the most prevalent neurological disease in aged people. Chronic cerebral hypoperfusion (CCH) is one of the causes of vascular dementia (VaD) and is also an etiological factor for Alzheimer's disease (AD). However, effective therapy for those two diseases is still missing. Resveratrol is a polyphenol produced by plants that have multiple biological functions, such as increased life span and delay in the onset of diseases associated with aging. It is known supplement with resveratrol could exert neuroprotection against multiple injury factors induced neuronal death and degeneration, as well as the cognitive decline of CCH rat model.. The morris water maze was used to evaluate the learning and memory, electrophysiological recording was used to detect the synaptic plasticity, the Golgi staining was used to examine the change of dendritic spines, the western blot was used to detect the proteins levels.. We reported that resveratrol pretreatment effectively restore the synaptic plasticity in CCH rats both functional and structural. We also found that the PKA-CREB activation may be a major player in resveratrol-mediated neuroprotection in CCH model.. Our data provide the mechanistic evidence for the neuroprotective effects of resveratrol in vascular dementia.

Topics: Animals; Carotid Stenosis; Cerebrovascular Circulation; Chronic Disease; Cyclic AMP; Cyclic AMP Response Element-Binding Protein; Cyclic AMP-Dependent Protein Kinases; Dementia, Vascular; Dendritic Spines; Dentate Gyrus; Enzyme Activation; Hypoxia-Ischemia, Brain; Learning Disabilities; Long-Term Potentiation; Male; Maze Learning; Memory Disorders; Nerve Tissue Proteins; Neuroprotective Agents; Random Allocation; Rats; Rats, Wistar; Resveratrol; Stilbenes

Moment-to-moment adjustment of cerebral blood flow (CBF) to neuronal activity via neurovascular coupling is essential for the maintenance of normal neuronal function. Increased oxidative stress that occurs with aging was shown to impair neurovascular coupling, which likely contributes to a significant age-related decline in higher cortical function, increasing the risk for vascular cognitive impairment. Resveratrol is a polyphenolic compound that exerts significant antiaging protective effects in large vessels, but its effects on the cerebromicrovasculature remain poorly defined. The present study was undertaken to investigate the capacity of resveratrol to improve neurovascular coupling in aging. In aged (24-mo-old) C57BL/6 mice N(ω)-nitro-l-arginine methyl ester-sensitive, nitric oxide-mediated CBF responses to whisker stimulation and to the endothelium-dependent dilator acethylcholine (ACh) were impaired compared with those in young (3-mo-old) mice. Treatment of aged mice with resveratrol rescued neurovascular coupling and ACh-induced responses, which was associated with downregulation of cortical expression of NADPH oxidase and decreased levels of biomarkers of oxidative/nitrative stress (3-nitrotyrosine, 8-isoprostanes). Resveratrol also attenuated age-related increases in reactive oxygen species (ROS) production in cultured cerebromicrovascular endothelial cells (DCF fluorescence, flow cytometry). In conclusion, treatment with resveratrol rescues cortical neurovascular coupling responses to increased neuronal activity in aged mice, likely by restoring cerebromicrovascular endothelial function via downregulation of NADPH oxidase-derived ROS production. Beneficial cerebromicrovascular effects of resveratrol may contribute to its protective effects on cognitive function in aging.

Topics: Aging; Animals; Cerebrum; Dementia, Vascular; Endothelium, Vascular; Male; Mice; Mice, Inbred C57BL; Microcirculation; NADPH Oxidases; Oxidative Stress; Reactive Oxygen Species; Resveratrol; Stilbenes; Vasodilation; Vasodilator Agents

Polydatin is one of the most common encountered stilbenes of nature and a key component of the Chinese herb Polygonum cuspidatum. This study is to investigate the effects of polydatin on learning and memory impairments induced by chronic cerebral hypoperfusion in rats, as well as the potential mechanism. Both common carotid arteries and both vertebral arteries occlusion (four-vessel occlusion, 4-VO) induced severe cognitive deficits tested by water maze task, along with oxidative stress in hippocampus. Oral administration of polydatin for 30 days markedly attenuated cognitive deficits compared with the control (p < 0.05). Biochemical determination revealed that polydatin decreased the production of malondialdehyde (MDA) and significantly increased the activities of superoxide dismutase (SOD) and catalase (CAT). Additionally, polydatin effectively alleviated the injuries of cultured neurons induced by oxygen-glucose deprivation (OGD). These results suggest that polydatin exhibit therapeutic potential for vascular dementia, which is most likely related, at least in part, to its anti-oxidant activity and the direct protection of neurons.

Topics: Animals; Catalase; Cells, Cultured; Dementia, Vascular; Disease Models, Animal; Drugs, Chinese Herbal; Fallopia japonica; Glucosides; Hippocampus; Learning; Male; Malondialdehyde; Maze Learning; Memory Disorders; Neurons; Neuroprotective Agents; Protective Agents; Rats; Rats, Sprague-Dawley; Stilbenes; Superoxide Dismutase