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Cerebral hypoperfusion plays a pivotal role in the ictus and development of vascular dementia (VaD) with neuropsychiatric symptoms. To date, few pharmacological interventions for neuropsychiatric symptoms are available in the VaD patients with neuropsychiatric impairments. Here, our results demonstrated that the extent of demyelination was dramatically deteriorated and the thickness of myelin sheath was evidently decreased in the presence of cerebral hypoperfusion, whereas Quercetin possessed the potential of abrogating these effects at least in part, then relieving anxiety and depression-like behavior when mice exposed to bilateral carotid artery stenosis (BCAS)/chronic restraint stress (CRS). The underlying mechanism was that Quercetin facilitated secretion of anti-inflammatory cytokines (IL-4 and IL-10) and in turn decreased production of pro-inflammatory factors (TNF-α and IL-1β) due to regulating microglial phenotype transformation, thereafter enhancing the microglial engulfment ability of myelin fragments in vitro and in vivo. Collectively, the results demonstrated that that Quercetin mediated microglial transformation into anti-inflammatory phenotype to reduce demyelination in ventral hippocampus (vHIP), thereafter mitigating neuropsychiatric deficits (including anxiety and depression). The present research broadens the therapeutic scope of Quercetin in central nervous system (CNS) disorders with presence of white matter damage and/or the insufficient activation of anti-inflammatory microglia, particularly for vascular dementia with/without neuropsychiatric symptoms. [ABSTRACT FROM AUTHOR]

Behavioral and psychological symptoms of dementia (BPSD) ubiquitously disturb all patients with dementia at some point in the disease course. Although a plethora of non-pharmacological and pharmacological methods targeting the relief BPSD have been developed, the therapeutic effect is still far from ideal. Here, a rat BPSD model combining the physiological changes with mental insults was successfully established. Meanwhile, our results indicated that TMP attenuated anxious behavior using an elevated plus maze (EPM) test, ameliorated recognitive ability and sociability through a novel object recognition test (NORT) and social interaction test (SIT), and improved learning and memory impairments via a Barnes maze in rats with bilateral common carotid arteries occlusion (BCCAO) plus chronic restraint stress (CRS). Given that hippocampus chronic cerebral hypoperfusion (CCH) always causes damage to the hippocampus, and the majority of cognitive impairments, behaviors, and stress responses are associated with pathology in the hippocampus including anxiety and depression, we paid attention to investigate the role of the hippocampus in BPSD. Our results indicated that Tetramethylpyrazine (TMP) attenuated anxiety and ameliorated recognitive ability, sociability, learning, and memory impairments due to alleviating dendritic and spine deficits, and upregulating the expression of synapse-related proteins (including PSD95, SYN, GAP43, SYP) in the hippocampus. We also found that the underlying mechanism was that TMP could activate the TrkB/ERK/CREB signaling pathway to promote synaptic remodeling in vivo and in vitro. Mechanically, the present study enlarges the therapeutic scope of TMP in neurodegenerative disorders and provides basic knowledge and feasible candidates for treating BPSD, particularly for vascular dementia. [ABSTRACT FROM AUTHOR]

We report a rare case of dysphagia characterized by extrinsic mechanical compression of the esophagus secondary to the highly tortuous anatomical variation in the descending thoracic aorta. [ABSTRACT FROM AUTHOR]