Uric acid is associated with vascular dementia in Chinese population.

OBJECTIVE: Mounting evidence suggests that oxidative stress is involved in the pathogenesis of vascular dementia (VD). Uric acid (UA) has long been implicated as a critical cause of cardiovascular disease. Nevertheless, UA was also expected to play an important role in antioxidant and neuroprotection recently. We hypothesized that UA may have a protective role against VD. The aim of this study was to investigate the link between serum UA and cognitive dysfunction in VD. MATERIALS AND METHODS: There were altogether 127 VD subjects and 81 nondemented controls enrolled in our study. Serum UA, demographic, and clinical characteristics were recorded at baseline, and all participants underwent Mini-Mental State Examination (MMSE) at the beginning of the trial. RESULTS: The VD group showed lower MMSE scores and serum UA levels than nondemented controls and there was significant statistical difference between the two groups (p < .05). Demographic and clinical characteristics such as age, gender, education, body mass index (BMI), total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), blood urea nitrogen (BUN), and serum creatinine (Scr) did not differ dramatically between groups (p > .05). In VD subjects, there was a positive correlation between serum UA and MMSE scores (r = .32, p < .05), and this correlation was independent of demographic and clinical characteristics (ß = .272, p < .05). CONCLUSIONS: VD subjects have dramatically lower serum UA levels in comparison to nondemented controls. Lower serum UA levels are linked to cognitive dysfunction and could serve as a potential predictor for VD.

Therapeutic Effect Analysis of Sinomenine on Rat Cerebral Ischemia-Reperfusion Injury.

OBJECTIVE: The objective of this study is to investigate the therapeutic effect of sinomenine (SIN) on rat cerebral ischemia-reperfusion (IR) injury and the molecular mechanism. METHODS: One hundred thirty-five rats were equally randomized into sham-operated group, middle cerebral artery occlusion (MCAO) group, and SIN group, and reversible rat MCAO model was made according to the Longa method for the MCAO and SIN groups. Then, 15 rats from each group were decapitated at 6, 12, and 24 hours after reperfusion to obtain brain tissue samples. Rats in the SIN group were injected with sinomenine by tail vein (90 mg/kg) 1 hour before ischemia; rats in the MCAO and sham-operated groups were administrated with the same volume of saline. Neurological severity score (NSS), infarction volume, ischemic brain water content, and blood-brain barrier (BBB) permeability were determined at corresponding time points. Acid-sensing ion channel (ASIC) 1a mRNA level was determined by quantitative real-time polymerase chain reaction; ischemic brain contents of lactic acid (LD), lactic dehydrogenase (LDH), ATPase, and inflammatory factors were determined by spectrophotometric method. RESULTS: At 12 hours after reperfusion and since then, NSS in the SIN group decreased obviously; infarction volume, brain water content, and BBB permeability in the SIN group were lower than those in the MCAO group (P < .05). IR injury resulted in the upregulation of the contents of ASIC1a mRNA, LD, LDH, and inflammatory factors and the downregulation of the contents of ATPase, while SIN could reverse the upregulation/downregulation effect induced by IR injury (P < .05). CONCLUSION: Through its anti-inflammation effect, which alleviates acidosis, improves energy metabolism, and inhibits ASIC1a level, SIN protects ischemic rat brain against cerebral IR injury.

Association between Helicobacter pylori infection and carotid atherosclerosis in patients with vascular dementia.

BACKGROUND AND PURPOSE: Accumulating evidence indicates that various infections contribute to the pathogenesis of atherosclerosis. Helicobacter pylori (Hp) has been implicated as a risk factor of atherosclerosis for stroke and other cardiovascular disease, but limited data exist regarding vascular dementia (VD). This study aimed to investigate the relationship between Hp infection and carotid atherosclerosis in patients with VD. METHODS: A total of 354 patients who were diagnosed with VD were enrolled. Patients were divided into Hp positive VD group (n=208) and Hp negative VD group (n=156) using the (13)C-urea breath test ((13)C-UBT). Serum YKL-40, a marker for inflammation, were analyzed by ELISA. Traditional atherosclerotic risk factors including age, gender, body mass index (BMI), total cholesterol (TC), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglycerides (TG), systolic blood pressure (SBP), diastolic blood pressure (DBP) and fasting blood glucose (FBG) were collected or detected. Carotid intima-media thickness (CIMT) was determined by color Doppler ultrasound. RESULTS: CIMT values and serum YKL-40 significantly increased in Hp positive VD group in comparison with Hp negative VD group (p<0.05). In Hp positive VD group, serum YKL-40 was positively correlated with CIMT (r=0.412, p<0.05), and the association was independent of traditional atherosclerotic risk factors (ß=0.381, p<0.001). CONCLUSIONS: CIMT and serum YKL-4 were significantly higher in Hp positive patients than Hp negative patients. Hp-induced inflammation may be a risk factor for atherosclerosis in patients with VD.

Is Helicobacter pylori infection a critical risk factor for vascular dementia?

PURPOSE: The association of Helicobacter pylori (Hp) infection and Alzheimer's disease has widely been addressed, but no relative data exist regarding vascular dementia (VD). The purpose of this study was to evaluate the relationship between Hp infection and VD. MATERIAL AND METHOD: From January 2014 to March 2015, patients at Tai'an City Central Hospital who were diagnosed with VD were included. Patients were divided into Hp positive and Hp negative group using the (13)C-urea breath test ((13)C-UBT). Three inflammatory cytokines including interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were detected. RESULTS: A total of 173 VD patients were included in the study. According to (13)C-UBT, 104 patients (60.1%) were Hp positive VD patients and 69 patients (39.9%) were Hp negative patients. No differences were found between Hp positive and Hp negative patients as regard to age, gender, body mass index, education level, hypertension, diabetes mellitus and hyperlipidemia (p > 0.05). Hp positive patients demonstrated significantly lower mean mini-mental state examination and Montreal cognitive assessment scores (p < 0.05) and higher plasma levels of IL-1ß, IL-6 and TNF-α than Hp negative patients (p < 0.05). CONCLUSIONS: Hp infection might contribute, at least in part, to the cognitive decline in patients with VD, and play a critical role possibly through increasing expression of IL-1ß, IL-6 and TNF-α.

Protective effects of p38 MAPK inhibitor SB202190 against hippocampal apoptosis and spatial learning and memory deficits in a rat model of vascular dementia.

Vascular dementia (VaD) is a common age-related neurodegenerative disease resulting from chronic hypoxia. In the present study, we examined the protective effects of p38 MAPK inhibitor SB202190 against hippocampal apoptosis and spatial learning and memory deficits in a chronic hypoperfusion rat model of VaD established by permanent bilateral carotid occlusion (2-VO). Sixty rats were randomly divided into sham-operated, VaD model, and VaD plus SB202190 groups (n = 20/group). After sham/2-VO surgery, rats were administered 0.1% DMSO (sham-operated and VaD groups) or SB202190 by intracerebroventricular injection. One week after inhibitor/vehicle treatment, hippocampal p38 MAPK phosphorylation was higher in the model group than in the SB202190 group (P < 0.01). Compared to the model group, the SB202190 group exhibited significantly shorter escape latencies in the Morris water maze hidden platform trials (P < 0.01) and longer times in the original platform quadrant during probe trials (P < 0.01). The SB202190 group also showed significantly reduced neuronal apoptosis in the hippocampus compared to VaD model rats (P < 0.01) as well as higher (antiapoptotic) Bcl-2 expression and lower (proapoptotic) caspase-3 expression (P < 0.01 for both). In conclusion, blockade of the p38 MAPK signaling pathway by SB202190 following permanent 2-OV reduced apoptosis of hippocampal neurons and rescued spatial learning and memory deficits.