Inhibition of the CEBPß-NFκB interaction by nanocarrier-packaged Carnosic acid ameliorates glia-mediated neuroinflammation and improves cognitive function in an Alzheimer's disease model.

Neuroinflammation occurs early in Alzheimer's disease (AD). The initial stage of AD is related to glial dysfunction, which contributes to impairment of Aß clearance and disruption of synaptic connection. CEBPß, a member of the CCAAT-enhancer-binding protein (CEBP) family, modulates the expression of inflammation-associated genes, and its expression is elevated in brains undergoing degeneration and injured brains. However, the mechanism underlying CEBPß-mediated chronic inflammation in AD is unclear. In this study, we observed that increases in the levels of nuclear CEBPß facilitated the interaction of CEBPß with the NFκB p65 subunit, increasing the transcription of proinflammatory cytokines in the APP/PS1 mouse brain. Oral administration of nanocarrier-packaged carnosic acid (CA) reduced the aberrant activation of microglia and astrocytes and diminished mature IL-1ß, TNFα and IL-6 production in the APP/PS1 mouse brain. CA administration reduced ß-amyloid (Aß) deposition and ameliorated cognitive impairment in APP/PS1 mice. We observed that CA blocked the interaction of CEBPß with NFκB p65, and chromatin immunoprecipitation revealed that CA reduced the transcription of the NFκB target genes TNFα and IL-6. We confirmed that CA alleviated inflammatory mediator-induced neuronal degeneration and reduced Aß secretion by inhibiting the CEBPß-NFκB signalling pathway in vitro. Sulfobutyl ether-beta-cyclodextrin (SBEßCD) was used as the encapsulation agent for the CA-loaded nanocarrier to overcome the poor water solubility and enhance the brain bioavailability of CA. The CA nanoparticles (NPs) had no obvious toxicity. We demonstrated a feasible SBEßCD-based nanodelivery system targeting the brain. Our data provide experimental evidence that CA-loaded NPs are potential therapeutic agents for AD treatment.

Correlation between fatigue and cognitive impairment and depression in patients with lacunar stroke: a retrospective case series study / 国际脑血管病杂志

Objective To investigate the correlation between fatigue and cognitive impairment and depression after lacunar stroke.Methods A total of 103 patients with lacunar infarction admitted from September 2009 to November 2010 were enrolled.Post-stroke fatigue was evaluated with the Fatigue Scale (FS-14) and the Fatigue Severity Scale (FSS-9); cognitive function was evaluated with the mini-mental state examination (MMSE) and the Montreal cognitive assessment (MoCA); and depression was evaluated with the self-rating depression scale (SDS) and the Hamilton Depression Rating Scale (HAMD).Results There were 34 patients (33.01％) (FSS-9) and 45 patients (43.69％) (FS-14) had fatigue.Of the 34 fatigue patients determined with FSS-9 scores,20 had cognitive impairment,26 had depression,and 16 had both cognitive impairment and depression.The Pearson correlation analysis showed that the FS-14 scores were siguificantly negatively correlated with the scores of MMSE (r =-0.307,P =0.002) and MoCA (r =-0.457,P=0.000),and significantly positively correlated with the scores of SDS (r =0.368,P =0.000) and HAMD (r =0.526,P =0.000); the FSS-9 scores were significantly negatively correlated with the scores of MMSE (r =-0.292,P=0.003) and MoCA (r=-0.340,P=0.000),and significantly positively correlated with the scores of SDS (r =0.403,P =0.000) and HAMD (r =0.564,P =0.000).Conclusions The incidence of fatigue,cognitive impairment and depression was higher.There was a certain correlation between fatigue and cognitive impairment and depression.