Cannabidiol improves the cognitive function of SAMP8 AD model mice involving the microbiota-gut-brain axis.

Cannabidiol (CBD), a natural component extracted from Cannabis sativa L. exerts neuroprotective, antioxidant, and anti-inflammatory effects in Alzheimer's disease (AD), a disease characterized by impaired cognition and accumulation of amyloid-B peptides (Aß). Interactions between the gut and central nervous system (microbiota-gut-brain axis) play a critical role in the pathogenesis of neurodegenerative disorder AD. At present investigations into the mechanisms underlying the neuroprotective action of CBD in AD are not conclusive. The aim of this study was thus to examine the influence of CBD on cognition and involvement of the microbiota-gut-brain axis using a senescence-accelerated mouse prone 8 (SAMP8) model. Data demonstrated that administration of CBD to SAMP8 mice improved cognitive function as evidenced from the Morris water maze test and increased hippocampal activated microglia shift from M1 to M2. In addition, CBD elevated levels of Bacteriodetes associated with a fall in Firmicutes providing morphologically a protective intestinal barrier which subsequently reduced leakage of intestinal toxic metabolites. Further, CBD was found to reduce the levels of hippocampal and colon epithelial cells lipopolysaccharide (LPS), known to be increased in AD leading to impaired gastrointestinal motility, thereby promoting neuroinflammation and subsequent neuronal death. Our findings demonstrated that CBD may be considered a beneficial therapeutic drug to counteract AD-mediated cognitive impairment and restore gut microbial functions associated with the observed neuroprotective mechanisms.

CSF high-mobility group box 1 is associated with drug-resistance and symptomatic etiology in adult patients with epilepsy.

PURPOSE: Extracellular high-mobility group box 1 (HMGB1) is considered a proinflammatory mediator and is involved in various neurological disorders. This study aims to determine the expression profiles of HMGB1 in cerebrospinal fluid (CSF) and paired serum, and to explore whether there is a relationship between CSF HMGB1 concentrations with seizure parameters in adult patients with epilepsy. METHODS: CSF and paired serum HMGB1 concentrations were measured in patients with drug-refractory epilepsy (DRE, n = 27), newly diagnosed epilepsy (NDE, n = 56), and other non-inflammatory neurological disorders (ONNDs, n = 22). The correlations in HMGB1 levels between CSF and blood were performed. The associations between HMGB1 levels and seizure parameters were analyzed. RESULTS: Mean (± SD) CSF HMGB1 concentrations were 5.08 ± 3.06, 3.03 ± 2.25, 0.83 ± 0.77 ng/mL in patients with DRE, NDE, and ONNDs, respectively. Corresponding mean (± SD) serum concentrations were 4.53 ± 2.81, 2.32 ± 1.54, 1.56 ± 0.84 ng/mL. The CSF HMGB1 concentrations were significantly higher in the DRE and NDE groups compared with the ONNDs group (p < 0.001). There were no correlations in HMGB1 levels between CSF and serum in the DRE, NDE, and ONNDs groups. Furthermore, patients with symptomatic etiology showed significantly high levels of CSF HMGB1. Patients without remission expressed elevated levels of CSF HMGB1 at one-year follow-up. Additionally, the CSF HMGB1 levels were positively associated with seizure frequency. CONCLUSION: Our study shows that HMGB1 may be a critical player in seizure mechanisms and CSF HMGB1 might be predictive in determining epilepsy etiology and prognosis.

Predicting seizure freedom with AED treatment in newly diagnosed patients with MRI-negative epilepsy: A large cohort and multicenter study.

OBJECTIVE: We developed and validated a prediction score for predicting the probability of 6-month and 12-month seizure freedom of antiepileptic drug (AED) treatment in newly diagnosed patients with magnetic resonance imaging (MRI)-negative epilepsy. METHODS: The development cohort included 543 consecutive patients from the Epilepsy Center of Henan Provincial People's Hospital, while the validation cohorts included 493 consecutive patients in two independent cohorts. Univariate analysis and a forward and backward elimination of multivariate Cox regression analysis were used to select predictive factors. The performance of the score was evaluated with C-index, calibration plots, and decision curve analysis. The risk stratification was also performed. RESULTS: The score included five routinely available predictors including Circadian rhythms, Electroencephalography before AED treatment, Neuropsychiatric disorders, Perinatal brain injury, and History of central nervous system infection (CENPH score). When applied to the external validation cohort, the score showed good discrimination with C-index (development group: 0.83; validation group: 0.78), and calibration plots indicated well calibration, as well as the decision curve analysis showed good predictive accuracy and clinical values in four cohorts. The points of the score were categorized to the following three probability levels for predicting seizure freedom: high probability (0-83.11 points), medium probability (83.11-122.71 points), and low probability (>122.71 points). And online calculator was established to make this score easily applicable in clinical practice. CONCLUSIONS: We established a simple, practical, and evidence-based prediction score for predicting seizure freedom with AEDs to aid in the clinical consultation and treatment decision for the newly diagnosed patients with MRI-negative epilepsy.

A scale for prediction of response to AEDs in patients with MRI-negative epilepsy.

OBJECTIVES: Antiepileptic drugs (AEDs) are the first choice in magnetic resonance imaging (MRI)-negative patients with epilepsy, although the responses to AEDs are diverse. Preoperative evaluation and postoperative prognosis in MRI-negative epilepsy have been reported. However, there are few tools for predicting the response to AEDs. Herein, we developed an AED response scale based on clinical factors and video-electroencephalography (VEEG) in MRI-negative patients with epilepsy. METHODS: A total of 132 consecutive patients with MRI-negative epilepsy at the Epilepsy Center of Henan Provincial People's Hospital between August 2016 and August 2018 were included. Patients were further divided into drug-responsive epilepsy ([DSE-MRI (-)]; n = 101) and drug-resistant epilepsy ([DRE-MRI (-)]; n = 31) groups. The clinical and VEEG factors were evaluated in univariate analyses and multivariate logistic regression analyses. A scale was derived and the scores categorized into 3 risk levels of DRE-MRI (-). RESULTS: A scale was established based on 4 independent risk factors for DRE-MRI (-). The scale had a sensitivity of 83.87%, specificity of 80.20%, positive likelihood ratio of 4.24, negative likelihood ratio of 0.20, and showed good discrimination with the area under the curve (AUC) of 0.886 (0.826-0.946). The categorization of the risk score based on this scale was: low risk (0-3 points), medium risk (3-5 points), and high risk (>5 points). CONCLUSION: We established a DRE-MRI (-) scale with a good sensitivity and specificity, which may be useful for clinicians when making medical decisions in patients with MRI-negative epilepsy.

High risk of anxiety and depression in caregivers of adult patients with epilepsy and its negative impact on patients' quality of life.

OBJECTIVE: The objective of this study was to assess the anxiety and depression of caregivers of adult patients with epilepsy (PWE) and evaluate its effect on patient quality of life (QOL). METHOD: One hundred sixty pairs of adult PWE and their caregivers were enrolled in our study. Quality of life in adult PWE was evaluated with the Quality of Life in Epilepsy Inventory-31 scale (QOLIE-31). Symptoms of anxiety and depression in caregivers were assessed with the Hamilton Anxiety Rating Scale (HAM-A) and the Hamilton Depression Rating Scale (HAM-D) respectively. Correlation and stepwise multiple liner regression analyses were used as statistical analysis. RESULTS: Of the caregivers, 41 (31.30%) had anxiety symptoms (HAM-A scores > 6) and 44 (33.59%) had depression symptoms (HAM-D scores > 6). Caregiver anxiety was significantly associated with poorer adult PWE QOL scores in four of the seven subscales and the QOLIE-31 total score. Caregiver depression was significantly associated with poorer adult PWE QOL in all seven subscales as well as the QOLIE-31 total score. Caregiver depression was an independent predictor of the QOLIE-31 total score and five subscales: seizure worry, emotional wellbeing, energy/fatigue, cognitive, and medication effects. CONCLUSION: Caregivers of adult PWE are at high risk of experiencing anxiety and depression. Caregiver psychological status, especially depression, was an independent predictor of poorer QOL for adult PWE.

Pressureless glass crystallization of transparent yttrium aluminum garnet-based nanoceramics.

Transparent crystalline yttrium aluminum garnet (YAG; Y3Al5O12) is a dominant host material used in phosphors, scintillators, and solid state lasers. However, YAG single crystals and transparent ceramics face several technological limitations including complex, time-consuming, and costly synthetic approaches. Here we report facile elaboration of transparent YAG-based ceramics by pressureless nano-crystallization of Y2O3-Al2O3 bulk glasses. The resulting ceramics present a nanostructuration composed of YAG nanocrystals (77 wt%) separated by small Al2O3 crystalline domains (23 wt%). The hardness of these YAG-Al2O3 nanoceramics is 10% higher than that of YAG single crystals. When doped by Ce3+, the YAG-Al2O3 ceramics show a 87.5% quantum efficiency. The combination of these mechanical and optical properties, coupled with their simple, economical, and innovative preparation method, could drive the development of technologically relevant materials with potential applications in wide optical fields such as scintillators, lenses, gem stones, and phosphor converters in high-power white-light LED and laser diode.