Hyperphosphorylation of Tau forming neurofibrillary tangles has been considered as a crucial event in the pathogenesis of Alzheimer's disease (AD). MiR-124-3p belongs to microRNA (miRNA) family and was markedly decreased in AD, however, the functions of miR-124-3p in the pathogenesis of AD remain unknown. We observed that the expression of miR-124-3p was significantly decreased in N2a/APP695swe cells; and transfection of miR-124-3p mimics not only attenuated cell apoptosis and abnormal hyperphosphorylation of Tau protein without any changes of total Tau protein, but also increased expression levels of Caveolin-1, phosphoinositide 3-kinase (PI3K), phospho-Akt (Akt-Ser473)/Akt, phospho-glycogen synthase kinase-3 beta (GSK-3β-Ser9)/GSK-3β in N2a/APP695swe cells. We further found that miR-12-3p directly targeted Caveolin-1; miR-124-3p inhibited abnormal hyperphosphorylation of Tau by regulating Caveolin-1-PI3K/Akt/GSK3β pathway in AD. This study reveals that miR-124-3p may play a neuroprotective role in AD, which may provide new ideas and therapeutic targets for AD.

Background: Neonatal bacterial meningitis is a severe infection with high mortality and morbidity. It is necessary to identify factors associated with a high risk of a poor prognosis so that we can prevent them with more appropriate treatments. This study was performed to summarize the prognostic factors known to predict adverse outcomes in neonatal bacterial meningitis.Methods: The Medline/PubMed, Cochrane Library and Embase databases were searched for studies of prognostic risk factors in neonates with bacterial meningitis. Studies published from the initiation of the database to April 30th, 2017 were included. The quality of cohort studies was assessed by the Newcastle-Ottawa Scale (NOS). The quality of cross-section studies was assessed by the Agency for Healthcare Research and Quality (AHRQ) scale. Each prognostic factor known to cause adverse outcomes is summarized.Results: Sixteen studies were identified, including 7 cohort studies and 9 cross section studies. Seizure and high protein levels in the cerebrospinal fluid (CSF) predict a poor prognosis in this disease. Coma, the need for ventilation support, and leukopenia also had some value for predicting poor prognoses. A bulging anterior fontanelle was valuable for predicting mortality. Low CSF glucose levels, thrombocytopenia, gestational age (GA) < 37 weeks and an altered sensorium were correlated with a poor prognosis. A birth weight < 2500 g, early onset meningitis and positive CSF cultures were correlated with mortality.Conclusions: This study provides a preliminary exploration of prognostic factors in neonatal bacterial meningitis and thereby fills some of the gaps in the study of prognoses in this disease. These prognostic factors can be used to predict and estimate outcomes in neonatal bacterial meningitis. Without a meta-analysis, the reliability of these factors cannot be assured. In addition, these results emphasize that there is an urgent need for a standardized protocol for follow-up and well-designed prognostic studies in neonatal bacterial meningitis.

Background: Neonatal seizures are a common neurological emergency in newborns. Phenobarbital (PB) is the first-line antiepileptic drug (AED). However, PB has some side effects, such as hypotension and respiratory depression, and it can accelerate neuronal apoptosis in the immature brain. Levetiracetam (LEV), a new antiepileptic drug, has been used as a second-line drug for the treatment of neonatal seizures. Compared with PB, LEV has many advantages, including a low incidence of side effects and better neurodevelopmental outcomes. However, there are only a few systematic reviews of LEV for the treatment of neonatal seizures.Objective: To evaluate the efficacy and safety of LEV for neonatal seizures and to compare the efficacy, side effects, and neurological outcomes between LEV and PB in the treatment of neonatal seizures.Methods: The keywords LEV, PB, and neonatal seizure were searched in the MEDLINE, Cochrane Library, Web of Science, EMBASE, clinicaltrials.gov, and China National Knowledge Internet (CNKI) databases with a last update in July 2021 to collect high-quality studies. We collected studies studying the efficacy or safety of LEV and PB in the treatment of neonatal seizures applying strict inclusion and exclusion criteria. The data were extracted and outcome measures, including efficacy, side effect rate, neurological score, and mortality rate, were analyzed with RevMan 5.3 software.Results: Ten articles were finally included in the meta-analysis. The meta-analysis showed that there was no difference in efficacy between LEV and PB in the treatment of neonatal seizures. Compared with PB, the incidence of side effects of LEV was lower. The incidence of hypotension and respiratory depression in the LEV group was significantly lower than that in the PB group. In terms of long-term neurodevelopmental outcomes, there was no significant difference in the Bayley Scales of Infant Development (BSID) scores between LEV and PB.Conclusion: PB is still the first-line AED recommended by the WHO for the treatment of neonatal seizures. The new AEDs LEV may not have better efficacy than PB. At the same time, LEV is associated with better neurodevelopment outcomes and a lower risk of adverse effects. In addition, continuous EEG monitoring should be used to diagnose neonatal seizures to evaluate the severity of the seizures, remission, and drug efficacy.Systematic Review Registration: PROSPERO, identifier: CRD42021279029.

Purpose. To review the recent neuroimaging studies on cognitive-behavioral therapy (CBT) for pain management, with the aim of exploring possible mechanisms of CBT. Recent Findings. Current studies can be divided into four categories, mixed pain, fibromyalgia, migraine, and experimental pain, based on the type of disease included, with the same or different changes of brain regions after CBT intervention. According to structural and functional MRI analyses, changes of brain gray matter volume, activation and deactivation of brain regions, and intrinsic connectivity between brain regions were observed after CBT sessions. The brain regions involved mainly included some areas related to cognitive and emotional regulation. After comparison, the DLPFC, OFC, VLPFC, PCC and amygdala were found to be recurrent in multiple studies and may be key regions for CBT intervention in pain management. In the treatment of mixed chronic pain, CBT may decrease the gray matter volume of DLPFC, reduce ICN connection of OFC within the DAN network, and increase fALFF of the PCC. For FM intervention, CBT may activate the bilateral OFC and VLPFC, while in migraine, only the right OFC, VLPFC, and DLPFC were found to be more activated after CBT. In addition, the differential action of the left and right amygdala has also been shown in the latest study of migraine. In heat-evoked pain, CBT may increase the deactivation of the PCC, the connectivity between the DMN and right VLPFC, while diminishing the deactivation of VLPFC. Summary. After CBT, the brain showed stronger top-down pain control, cognitive reassessment, and altered perception of stimulus signals (chronic pain and repeated acute pain). The DLPFC, OFC, VLPFC, PCC, and amygdala may be the key brain regions in CBT intervention of pain.

PurposeTo investigate the effect of sleep disorder (SD) on the changes of brain network dysfunction in mild cognitive impairment (MCI), we compared network connectivity patterns among MCI, SD, and comorbid MCI and sleep disorders (MCI-SD) patients using resting state functional magnetic resonance imaging (RS-fMRI).Patients and MethodsA total of 60 participants were included in this study, 20 each with MCI, SD, or MCI-SD. And all participants underwent structural and functional MRI scanning. The default-mode network (DMN) was extracted by independent component analysis (ICA), and regional functional connectivity strengths were calculated and compared among groups.ResultsCompared to MCI patients, The DMN of MCI-SD patients demonstrated weaker functional connectivity with left middle frontal gyrus, right superior marginal gyrus, but stronger connectivity with the left parahippocampus, left precuneus and left middle temporal gyrus. Compared to the SD group, MCI-SD patients demonstrated weaker functional connectivity with right transverse temporal gyrus (Heschl’s gyrus), right precentral gyrus, and left insula, but stronger connectivity with posterior cerebellum, right middle occipital gyrus, and left precuneus.ConclusionPatients with MCI-SD show unique changes in brain network connectivity patterns compared to MCI or SD alone, likely reflecting a broader functional disconnection and the need to recruit more brain regions for functional compensation.