Kang Huo

Sleep Deprivation Induced Plasma Amyloid-β Transport Disturbance in Healthy Young Adults

BACKGROUND Sleep is an important physiological process and beneficial in the removal of brain metabolites and functional recovery. Prior studies have shown that sleep disorders are significant risk factors for Alzheimers disease (AD). OBJECTIVE The present study was designed to characterize the effect of short-term total sleep deprivation (TSD) on plasma amyloid-β (Aβ) concentrations. METHODS A clinical trial was conducted between March 1, 2016, and April 1, 2016. Twenty volunteers (age 27.3±3.4 years) with normal cognitive function and sleeping habits were recruited from the local population. Participants underwent 24 h of TSD. Periprocedural blood samples were collected to compare the changes of plasma Aβ42, Aβ40, low-density lipoprotein receptor-related protein (sLRP-1), soluble receptors for advanced glycation end products (sRAGE), and serum superoxide dismutase (SOD) and malonaldehyde (MDA). RESULTS TSD increased morning plasma Aβ40 levels by 32.6% (p < 0.001) and decreased the Aβ42/Aβ40 ratio by 19.3% (p < 0.001). A positive relationship was found between TSD duration and plasma Aβ40 level (r = 0.51, p < 0.001) and Aβ40/Aβ42 ratio (r = 0.25, p = 0.003). Plasma concentrations of sLRP1 (p = 0.018) and sRAGE (p = 0.001) decreased significantly after TSD. Aβ40 and Aβ42 plasma concentrations correlated with plasma levels of sLRP1 and sRAGE. Serum SOD decreased after TSD (p = 0.005), whereas serum MDA was increased (p = 0.001). CONCLUSION Sleep deprivation can lead to an elevation of plasma Aβ40 and decrease of the Aβ42/Aβ40 ratio. The underlying mechanisms may be related to increased oxidative stress and impaired peripheral Aβ clearance as pathomechanisms of AD.

Autophagy-lysosome dysfunction is involved in Aβ deposition in STZ-induced diabetic rats

HighlightsIn this research, these findings indicated that diabetes activated autophagy, but lysosome function was impaired.Autophagy‐lysosome dysfunction may be involved in the A&bgr; deposition in diabetic cognitive impairment.As the time advanced, the A&bgr; deposition was getting worse in hippocampus of diabetic rats. ABSTRACT &bgr;‐Amyloid (A&bgr;) deposition has a central role in the pathogenesis of Alzheimer disease (AD). Previous studies have indicated that as a risk factor for AD, diabetes mellitus (DM) could induce A&bgr; deposition in the brain, but the mechanism is not fully elucidated. Autophagy‐lysosome is a cellular pathway involved in protein and organelle degradation. In the present study, we used streptozotocin (STZ)‐induced diabetic rats to investigate whether autophagy‐lysosome is related to A&bgr;1‐42 clearance in DM. We found that DM rats had a longer escape latency and less frequent entry into the target zone than that of the control group (p < 0.05) in the Morris water maze test. Meanwhile, hippocampal neuron damage and apoptosis (p < 0.05) were found in the DM rats. The A&bgr;1‐42 expression in the hippocampus significantly increased in the DM group compared with the control group (p < 0.05). The markers of autophagy, beclin‐1 and LC3 II, were increased (p < 0.05), whereas LC3 I was decreased (p < 0.05), and the ratio of LC3 II / I was increased as the time advanced (p < 0.01). LAMP1 and LAMP2, which are the markers of lysosome function, were decreased in the hippocampus of DM rats (p < 0.05). The A&bgr;1‐42 deposition was correlated with beclin‐1, LC3 II, and LC3 I positively (p < 0.05), but with LAMP1 and LAMP2 negatively (p < 0.05). These findings indicate that DM activated autophagy, but lysosome function was impaired. Autophagy‐lysosome dysfunction may be involved in the A&bgr; deposition in diabetic cognitive impairment.

Association between platelet distribution width and poor outcome of acute ischemic stroke after intravenous thrombolysis

Purpose The platelet distribution width (PDW) reflects the status of platelet activity and may be useful for early predictions of the clinical outcome of stroke patients. The purpose of the study was to determine the associations between PDW and clinical outcomes after intravenous thrombolysis in stroke patients. Patients and methods Acute ischemic stroke patients who received intravenous treatment with recombinant tissue-type plasminogen activator were selected for inclusion in the retrospective cohort of this study. The relations between PDW at admission and clinical outcomes were analyzed, including a poor outcome as assessed using the modified Rankin Scale at 3 months, early neurological improvement, and any hemorrhage. The effect of PDW at admission on a poor outcome at 3 months was analyzed using a multivariable logistic regression model with adjustment for potential confounders. The optimal PDW cutoff for predicting poor outcome at 3 months was determined by analyzing the receiver operating characteristics curve. Results PDW was significantly higher for a good outcome than a poor outcome (p=0.005), with median (interquartile range) values of 16.2 (13.2–17.2) and 13.6 (12.5–15.9), respectively. PDW was also higher in patients with early neurological improvement than in patients without improvement (p=0.020) and did not differ between hemorrhage and nonhemorrhage patients. The association between PDW <16.05% and poor outcome remained in a multivariable logistic regression analysis, with an OR of 6.68 and a 95% CI of 1.69–26.49 (p=0.007). Conclusion Results suggest a novel hypothesis that a lower PDW may be related with a poor outcome at 3 months after intravenous thrombolysis in acute ischemic stroke patients.

Right-to-left shunt may be prone to affect the white matter integrity of posterior circulation in migraine without aura

Numerous studies have indicated an association between migraine and right-to-left shunt. However, little is known about whether right-to-left shunt has an effect on the migraine brain. This observational study aims to explore the impact of right-to-left shunt on the brain of migraine without aura on microstructural level. Thirty-five patients with migraine without aura were enrolled in this study. Contrast-enhanced Transcranial Doppler was performed to evaluate the status of right-to-left shunt. Three-dimensional T1-weighted and diffusion tensor images were acquired for data analysis. We employed voxel-based morphometry and tract-based spatial statistical analyses to assess the differences of gray and white matter between migraineurs with and without right-to-left shunt, respectively. Among the 35 patients, 19 (54.3%) patients had right-to-left shunt. There were no significant differences in headache features between migraineurs with and without right-to-left shunt. There were significant increases of mean and radial diffusivity in migraineurs with right-to-left shunt compared with migraineurs without right-to-left shunt. The alterations were primarily located in the right posterior thalamic radiation, secondly in the body of corpus callosum and the right superior corona radiata. No significant differences were observed in values of fractional anisotropy and axial diffusivity. No significant between-group differences were found in gray matter volume. Right-to-left shunt may cause alterations of white matter integrity in migraine without aura, and the alterations are more likely to be located at the posterior circulation.

De Ritis ratio (AST/ALT) as an independent predictor of poor outcome in patients with acute ischemic stroke.

Purpose The aspartate transaminase/alanine transaminase ratio (De Ritis ratio, AAR) was reported to be associated with patients’ prognosis in certain diseases recently. The objective of the current study was to determine the association between the AAR at admission and poor outcome at 3 months in acute ischemic stroke (AIS) patients. Patients and methods This retrospective cohort study included patients who experienced their first-ever AIS between June 2015 and March 2016. The primary outcome measure was a poor outcome at 3 months (modified Rankin Scale score >2). Multivariate logistic regression models were used to assess the relationship between AAR quartiles and clinical outcomes among the AIS patients. Receiver operating characteristic curve analysis was applied to identify the optimal cutoff for AAR in predicting the prognosis of AIS. Results In terms of the relationship between poor outcome and AAR, the adjusted odds ratio comparing the highest and lowest AAR quartiles was 2.15 (95% confidence interval =1.14–4.05). An AAR of 1.53 was identified as the optimal cutoff. In a prespecified subgroup analysis according to the time from symptom onset to treatment (>24 vs ≤24 hours), there was no significant difference in the effect of AAR >1.53 between the two groups. Conclusion An increased AAR at admission is significantly associated with a poor outcome at 3 months in AIS patients.