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.
ObjectiveMounting 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 MethodsThere 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.ResultsThe 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 (β = .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.
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-1β, IL-6 and TNF-α.
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