Medical Histories of Control Subjects Influence the Biomarker Potential of Plasma Aβ in Alzheimer’s Disease: a Meta-analysis

Whether blood amyloid-β (Aβ) could be a peripheral biomarker of Alzheimer’s disease (AD) remains in dispute. In the present study, we conducted a meta-analysis with 19 citations searched from Embase, PubMed, and the Cochrane Library database. Weighted mean difference (WMD) with 95% confidence intervals (CIs) was used to estimate the effect size. We firstly analyzed the plasma Aβ40, Aβ42, and Aβ42/Aβ40 ratio in AD and control group subjects. However, only a lower level of plasma Aβ42 was figured out in AD group subjects with weak statistical significance (WMD 1.82; 95% CI 0.59, 3.06; P = 0.004; I2 = 84%). We considered that the medical histories of control subjects could influence the biomarker ability of plasma Aβ. Therefore, subgroup analyses were then carried out based on a new recruiting criterion for control subjects, defining as no afflictions of any Aβ-related diseases. Surprisingly, AD group subjects showed a significant decrease in plasma Aβ42/Aβ40 ratio with low heterogeneity among studies (WMD 0.02; 95% CI 0.02, 0.02; P < 0.00001; I2 = 0%). Moreover, not only the Aβ42/Aβ40 ratio but also Aβ42 and Aβ40 were indifferent between AD and pseudo-control subjects which might be afflicted with Aβ-related diseases. This meta-analysis demonstrated that medical histories of control subjects were interference factors impeding plasma Aβ to be a biomarker of AD.     

Correction to: Limb Remote Ischemic Preconditioning Reduces Repeated Ketamine Exposure-Induced Adverse Effects in the Developing Brain of Rats

Journal of Molecular Neuroscience - The original version of this article unfortunately contained mistakes in Fig.&nbsp;2c, d and Funding section.     

Melatonin reduces oxidative stress and improves vascular function in pulmonary hypertensive newborn sheep

Pulmonary hypertension of the newborn (PHN) constitutes a critical condition with severe cardiovascular and neurological consequences. One of its main causes is hypoxia during gestation, and thus, it is a public health concern in populations living above 2500 m. Although some mechanisms are recognized, the pathophysiological facts that lead to PHN are not fully understood, which explains the lack of an effective treatment. Oxidative stress is one of the proposed mechanisms inducing pulmonary vascular dysfunction and PHN. Therefore, we assessed whether melatonin, a potent antioxidant, improves pulmonary vascular function. Twelve newborn sheep were gestated, born, and raised at 3600 meters. At 3 days old, lambs were catheterized and daily cardiovascular measurements were recorded. Lambs were divided into two groups, one received daily vehicle as control and another received daily melatonin (1 mg/kg/d), for 8 days. At 11 days old, lung tissue and small pulmonary arteries (SPA) were collected. Melatonin decreased pulmonary pressure and resistance for the first 3 days of treatment. Further, melatonin significantly improved the vasodilator function of SPA, enhancing the endothelial‐ and muscular‐dependent pathways. This was associated with an enhanced nitric oxide‐dependent and nitric oxide independent vasodilator components and with increased nitric oxide bioavailability in lung tissue. Further, melatonin reduced the pulmonary oxidative stress markers and increased enzymatic and nonenzymatic antioxidant capacity. Finally, these effects were associated with an increase of lumen diameter and a mild decrease in the wall of the pulmonary arteries. These outcomes support the use of melatonin as an adjuvant in the treatment for PHN.     

Melatonin alleviates brain injury in mice subjected to cecal ligation and puncture via attenuating inflammation,apoptosis, and oxidative stress: the role of SIRT1 signaling

Sepsis is a systemic inflammatory response to infection that causes severe neurological complications. Previous studies have suggested that melatonin is protective during sepsis. Additionally, silent information regulator 1 (SIRT1) was reported to be beneficial in sepsis. However, the role of SIRT1 signaling in the protective effect of melatonin against septic encephalopathy remains unclear. This study aimed to investigate the role of SIRT1 in the protective effect of melatonin. EX527, a SIRT1 inhibitor, was used to reveal the role of SIRT1 in melatonin's action. Cecal ligation and puncture or sham operation was performed in male C57BL/6J mice. Melatonin was administrated intraperitoneally (30 mg/kg). The survival rate of mice was recorded for the 7‐day period following the sham or CLP operation. The blood–brain barrier (BBB) integrity, brain water content, levels of inflammatory cytokines (TNF‐α, IL‐1β, and HMGB1), and the level of oxidative stress (superoxide dismutase (SOD), catalase (CAT), and malondialdehyde (MDA)) and apoptosis were assessed. The expression of SIRT1, Ac‐FoxO1, Ac‐p53, Ac‐NF‐κB, Bcl‐2, and Bax was detected by Western blot. The results suggested that melatonin improved survival rate, attenuated brain edema and neuronal apoptosis, and preserved BBB integrity. Melatonin decreased the production of TNF‐α, IL‐1β, and HMGB1. Melatonin increased the activity of SOD and CAT and decreased the MDA production. Additionally, melatonin upregulated the expression of SIRT1 and Bcl‐2 and downregulated the expression of Ac‐FoxO1, Ac‐p53, Ac‐NF‐κB, and Bax. However, the protective effects of melatonin were abolished by EX527. In conclusion, our results demonstrate that melatonin attenuates sepsis‐induced brain injury via SIRT1 signaling activation.     

Effects and Safety of Magnesium Sulfate on Neuroprotection: A Meta-analysis Based on PRISMA Guidelines

To evaluate the evidence of effects and safety of magnesium sulfate on neuroprotection for preterm infants who had exposure in uteri.We searched electronic databases and bibliographies of relevant papers to identify studies comparing magnesium sulfate (MgSO₄) with placebo or other treatments in patients at high risk of preterm labor and reporting effects and safety of MgSO₄ for antenatal infants. Then, we did this meta-analysis based on PRISMA guideline. The primary outcomes included fatal death, cerebral palsy (CP), intraventricular hemorrhage, and periventricular leukomalacia. Secondary outcomes included various neonatal and maternal outcomes.Ten studies including 6 randomized controlled trials and 5 cohort studies, and involving 18,655 preterm infants were analyzed. For the rate of moderate to severe CP, MgSO₄ showed the ability to reduce the risk and achieved statistically significant difference (odd ratio [OR] 0.61, 95% confidence interval [CI] 0.42–0.89, P = 0.01). The comparison of mortality rate between the MgSO4 group and the placebo group only presented small difference clinically, but reached no statistical significance (OR 0.92, 95% CI 0.77–1.11, P = 0.39). Summarily, the analysis of adverse effects on babies showed no margin (P > 0.05). Yet for mothers, MgSO₄ exhibited obvious side-effects, such as respiratory depression, nausea and so forth, but there exited great heterogeneity.MgSO₄ administered to women at high risk of preterm labor could reduce the risk of moderate to severe CP, without obvious adverse effects on babies. Although there exit many unfavorable effects on mothers, yet they may be lessened through reduction of the dose of MgSO₄ and could be tolerable for mothers. So MgSO₄ is both beneficial and safety to be used as a neuroprotective agent for premature infants before a valid alternative was discovered.