Plasma levels of ceramides relate to ischemic stroke risk and clinical severity.

Recent studies have suggested that specific plasma ceramides are independently associated with atherosclerosis and cardiovascular diseases, but it is currently unknown whether plasma ceramide levels are associated with ischemic stroke. Here, we examined whether ceramides were associated with both ischemic stroke risk and clinical severity at admission. We measured three previously identified high-risk plasma ceramide molecules [Cer(d18:1/16:0), Cer(d18:1/22:0), and Cer(d18:1/24:0)] in 202 patients with acute ischemic stroke and 202 age and sex matched control cases. Plasma ceramides levels were measured by a targeted liquid chromatography-tandem mass spectrometry assay at baseline. The median age of the 202 stroke patients was 66 (interquartile range [IQR], 58-75) years and 54.0 % were men. Plasma levels of C16:0, C22:0, and C24:0 ceramides in stroke patients were significantly higher than in those control cases (P < 0.001, all). In multivariate logistic regression analysis adjusted for other risk factors, higher levels of C16:0, C22:0, and C24:0 ceramides were associated with higher risk of ischemic stroke (odd ratio [OR] for one IQR increase: 2.15[1.42-2.99]; 2.90[2.13-4.01] and 1.29[1.10-1.69]; respectively). At admission, 103 patients (51.0 %) had a minor stroke (NIHSS < 6). In these patients, plasma levels of C16:0, C22:0, and C24:0 ceramides were lower than that observed in patients with moderate-to-high clinical severity (P < 0.001, all). In multivariate logistic regression analysis adjusted for other risk factors, higher levels of C16:0, C22:0, and C24:0 ceramides were associated with higher risk of moderate-to-high stroke (OR for one IQR increase: 2.96 [2.05-4.22], 3.03 [2.01-4.25] and 1.72 [1.25-3.31], respectively). An elevated plasma levels of ceramides were predictors of both risk and severity at admission in ischemic stroke patients. The underlying mechanisms of these associations remain to be investigated.

N-Butylphthalide (NBP) ameliorated cerebral ischemia reperfusion-induced brain injury via HGF-regulated TLR4/NF-κB signaling pathway.

N-Butylphthalide (NBP) has been known to have potential neuroprotective effects in Alzheimer's disease and stroke animal models. Hepatocyte-growth factor (HGF), with strong angiogenic properties, exerted protective role in brain injury. The present study was aimed to investigate the possible anti-inflammatory effects of NBP on the brain injury of rats with cerebral ischemia reperfusion (IR) and astrocytes activation induced by lipopolysaccharide (LPS) treatment. Our results showed that cerebral IR induced brain damage with down-regulation of HGF and astrocytes activation. NBP treatment significantly increased HGF expression and activated cMet/PI3K/AKT signaling pathway, stimulating mTOR activity and suppressing apoptosis in brain tissues. Also NBP inhibited pro-inflammatory cytokines expression, including IL-6, IL-1ß, and TNFα, via TLR4/NF-κB suppression. Anti-HGF treatment enhanced TLR4 expression while HGF could suppress TLR4 activation and its down-streaming signals, attenuating inflammation finally. Notably, NBP up-regulated HGF and down-regulated TLR4 expression significantly in the astrocytes combined with the treatment of TLR4 inhibitor than the cells only treated with TLR4 inhibitor, suggesting that NBP could further suppress TLR4 activation, suggesting that NBP might impede TLR4 through up-regulating HGF expression. These results suggested that NBP treatment significantly ameliorated cerebral IR-induced brain injury by inhibiting TLR4/NF-κB-associated inflammation regulated by HGF.