关键词： Moderate traumatic brain injury   Restraint stress   Endoplasmic reticulum stress   Neurodegeneration   Neurological impairments  

摘要： Based on accumulating evidence, patients recovering from mild and moderate traumatic brain injury (TBI) often experience increased sensitivity to stressful events. However, few studies have assessed on the effects and pathophysiological mechanisms of stress on TBI. In the current study, using a mouse model of moderate TBI, we investigated whether restraint stress (RS) regulates secondary neurodegeneration and neuronal cell death, which are commonly associated with neurological dysfunctions. Our data showed that RS significantly reduced body weight recovery, delayed the recovery of neurological functions (motor function, cognitive function and anxiety-like behavior) and exacerbated the brain lesion volume after moderate TBI. Immunofluorescence results indicated that moderate TBI-induced cell insults and blood-brain barrier leakage were aggravated by RS. Further Western blotting experiments showed that RS activated endoplasmic reticulum (ER) stress excessively after moderate TBI and decreased the number of NeuN-positive cells, but increased the number of CHOP/NeuN-co-positive cells by performing immunostaining in the injured cortex after moderate TBI. Moreover, RS increased the ratios of CHOP/A beta and CHOP/p-Tau co-positive cells in the injured cortex after moderate TBI. However, blocking ER stress with the classic ER stress inhibitor salubrinal remarkably decreased apoptosis and the levels of autophagy-related proteins in the mouse model of moderate TBI plus RS. Collectively, RS delays the recovery of neurological function and deteriorates morphological damage by excessively activating ER stress-mediated neurodegeneration, apoptosis and autophagy after moderate TBI. Thus, monitoring stress levels in patients recovering from non-severe TBI may merit consideration in the future.

摘要： Background Repeat expansion disorders affect about 1 in 3000 individuals and are clinically heterogeneous diseases caused by expansions of short tandem DNA repeats. Genetic testing is often locus-specific, resulting in underdiagnosis of people who have atypical clinical presentations, especially in paediatric patients without a previous positive family history. Whole genome sequencing is increasingly used as a first-line test for other rare genetic disorders, and we aimed to assess its performance in the diagnosis of patients with neurological repeat expansion disorders. Methods We retrospectively assessed the diagnostic accuracy of whole genome sequencing to detect the most common repeat expansion loci associated with neurological outcomes (AR, ATN1, ATXN1, ATXN2, ATXN3, ATXN7, C9orf72, CACNA1A, DMPK, FMR1, FXN, HTT, and TBP) using samples obtained within the National Health Service in England from patients who were suspected of having neurological disorders;previous PCR test results were used as the reference standard. The clinical accuracy of whole genome sequencing to detect repeat expansions was prospectively examined in previously genetically tested and undiagnosed patients recruited in 2013-17 to the 100 000 Genomes Project in the UK, who were suspected of having a genetic neurological disorder (familial or early-onset forms of ataxia, neuropathy, spastic paraplegia, dementia, motor neuron disease, parkinsonian movement disorders, intellectual disability, or neuromuscular disorders). If a repeat expansion call was made using whole genome sequencing, PCR was used to confirm the result. Findings The diagnostic accuracy of whole genome sequencing to detect repeat expansions was evaluated against 793 PCR tests previously performed within the NHS from 404 patients. Whole genome sequencing correctly classified 215 of 221 expanded alleles and 1316 of 1321 non-expanded alleles, showing 97.3% sensitivity (95% CI 94.2-99.0) and 99.6% specificity (99.1-99.9) across the

关键词： Spinal cord injury   Sex differences   Functional recovery   Neuroinflammation  

摘要： Whereas human spinal cord injury (SCI) is more common in men, the prevalence is growing in women. However, little is known about the effect of biological sex on brain dysfunction and injury mechanisms. To model the highest per capita rate of injury (ages between 16 and 30 years old) in humans, in the present study, young adult or a young/middle-aged male and female C57BL/6 mice were subjected to moderate contusion SCI. When mice were injured at 10-12-week-old, transcriptomic analysis of inflammation-related genes and flow cytometry revealed a more aggressive neuroinflammatory profile in male than females following 3 d SCI, ostensibly driven by sex-specific changes myeloid cell function rather than cell number. Female mice were generally more active at baseline, as evidenced by greater distance traveled in the open field. After SCI, female mice had more favorable locomotor function than male animals. At 13 weeks post-injury, male mice showed poor performance in cognitive and depressive-like behavioral tests, while injured female mice showed fewer deficits in these tasks. However, when injured at 6 months old followed by 8 months post-injury, male mice had considerably less inflammatory activation compared with female animals despite having similar or worse outcomes in affective, cognitive, and motor tasks. Collectively, these findings indicate that sex differences in functional outcome after SCI are associated with the age at onset of injury, as well as disrupted neuroinflammation not only at the site of injury but also in remote brain regions. Thus, biological sex should be considered when designing new therapeutic agents.

关键词： intestinal bacteria   neurodegenerative diseases   tea polyphenols  

摘要： Tea polyphenols (TP) are one of the most functional and bioactive substances in tea. The interactions between TP and intestinal microbiota suggest that probiotics intervention is a useful method to ameliorate neurological diseases. Now, numerous researches have suggested that TP plays a significant role in modulating intestinal bacteria, especially in the area of sustaining a stable state of intestinal microbial function and abundance. Furthermore, homeostatic intestinal bacteria can enhance the immunity of the host. The close reciprocity between intestinal microbiota and the central nervous system provides a new chance for TP to modulate neural-related diseases depending on intestinal microbiota. Therefore, based on the bidirectional relationship between the brain and the intestines, this review provides a new clue to solve insomnia symptoms and related neurological diseases that will enable us to better study the bidirectional effects of TP and intestinal microbiota on the improvement of host health. Practical applications This review provides a new clue to solve insomnia symptoms and related neurological diseases that will enable us to better study bidirectional effects of TP and intestinal microbiota on the improvement of host health.

关键词： Mesenchymal stromal cell (MSC)   Extracellular vesicles   Exosomes  

摘要： Cell-based therapy using Mesenchymal Stromal Cell (MSC) has generally been efficacious in treating a myriad of diseases in animal models and clinical trials. The rationale for MSC therapy was predicated on the potential of MSC to differentiate and form new replacement cells in the diseased tissue. However, pre-clinical animal and clinical data were more consistent with a secretion- and not a differentiation-based rationale. Analysis of MSC secretion led to the identification of small extracellular vesicles (sEVs) as therapeutically active, secretory agents. MSC-sEVs are defined as bi-lipid membrane vesicles of 50-200 nm in diameter that are secreted by MSCs. They reportedly exert similar therapeutic efficacy as MSCs in many diseases including neurological diseases. MSC-sEVs being small and non-living are intrinsically safer than living MSCs. Manufacturing of MSC-sEVs may also be less complex. Nevertheless, realising the therapeutic potential of MSC-sEVs will require exacting scientific rigor and robustness, as well as compliance to regulatory oversight. This review summarises the scientific rationale for the transition of MSC therapy from a cell- to an EV-based therapy and discusses critical scientific issues in the development of MSC-sEVs therapy.

关键词： Intravenous immunoglobulin   Autoimmune neurological diseases   meta-analysis  

摘要： Background: Corticosteroids are the first-line treatment for several common autoimmune neurological diseases. Other therapeutic approaches, including intravenous immunoglobulin (IVIg) and plasmapheresis, have shown mixed results in patient improvement. Objective: To compare the efficacy of IVIg administration with that of corticosteroids, plasmapheresis, and placebo in autoimmune neurological diseases like Guillain-Barre acute accent syndrome, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, optic neuritis, and multiple sclerosis. Methods: A systematic review was performed on the databases PubMed, MEDLINE, Embase, and Cochrane. Controlled, randomized studies comparing the efficacy of IVIg with placebo, plasmapheresis, and/or glucocorticoid administration were selected. Only studies reporting the number of patients who improved after treatment were included, irrespective of language or publication year. In total, 23 reports were included in the meta analysis ***: Our meta-analysis showed a beneficial effect of IVIg administration on patient improvement over placebo (OR = 2.79, CI [95%] = 1.40-5.55, P = 0.01). Meanwhile, IVIg administration showed virtually identical effects to plasmapheresis (OR = 0.83, CI [95%] = 0.45-1.55, P < 0.01). Finally, no significant differences were found in the efficacy of IVIg and glucocorticoid administration (OR = 0.98, Cl [95%] = 0.58-1.68, P = 0.13). Conclusion: IVIg can be regarded as a viable therapeutic approach, either as a first-or second-line therapy, and as an adjuvant therapy for autoimmune neurological diseases.

关键词： coronavirus   COVID-19   COVID-19 vaccine   facial nerve palsy   Guillain-Barre syndrome   neurological events  

摘要： The coronavirus disease 2019 (COVID-19) pandemic has affected millions of individuals worldwide. The global scientific effort to design an effective vaccine against this virus has led to the development of several vaccine candidates. The expedited rollout of these vaccines has created some public distrust regarding the safety of these new vaccines. This review compiles clinical data from reports of diagnosed immune-related neurological events that have occurred after COVID-19 vaccine administration with the exception of those secondary to hematological abnormalities. A systematic literature search was performed, using several databases, to identify reports of postvaccination adverse neurological events. The search resulted in 18 studies that met our criteria. These studies included 61 patients who had received COVID-19 vaccines and experienced at least 1 neurological adverse effect. The most common neurological event was facial nerve palsy (50% of all events). Other less frequently reported events included the reactivation of herpes zoster, Guillain-Barre syndrome, other demyelinating diseases, and neuropathy. The underlying mechanism was hypothesized to be related to vaccine-induced type 1 interferon production leading to decreased tolerance of the myelin sheath antigens. Other hypotheses include vaccine-induced transient lymphopenia and immune dysregulation. Most of the reported events were time limited and resolved spontaneously. Given the rarity of reported neurological events compared to the total number of vaccines administered, and the similarity in the incidence of events between COVID-19 vaccines and other more common vaccines, there is little evidence to support a causal relationship between COVID-19 vaccines and adverse neurological events.

关键词： amperometry   field-effect transistors   flexible electronics   multiplexed sensing   potentiometry  

摘要： The continuous, real-time, and concurrent detection of multiple biomarkers in bodily fluids is of high significance for advanced healthcare. While active, semiconductor-based biochemical sensing platforms provide levels of functionality exceeding those of their conventional passive counterparts, the stability of the active biosensors in the liquid environment for continuous operation remains a challenging topic. This work reports the development of a class of flexible and waterproof field-effect transistor arrays for multiplexed biochemical sensing. In this design, monolithic, ultrathin, dense, and low defect nanomembranes consisting of monocrystalline Si and thermally grown SiO2 simultaneously serve as high-performance backplane electronics for signal transduction and stable biofluid barriers with high structural integrity due to the high formation temperature. Coupling the waterproof transistors with various ion-selective membranes through the gate electrode allows for sensitive and selective detection of multiple ions as biomarkers for traumatic brain injury. The study also demonstrates a similar encapsulation structure which enables the design of waterproof amperometric sensors based on this materials strategy and integration scheme. Overall, key advantages in flexibility, stability, and multifunctionality highlight the potential of using such electronic sensing platforms for concurrent, continuous detection of various neurological biomarkers, proving a promising approach for early diagnosis and intervention of chronic diseases.

关键词： Burnout   Neurology residents   Coronavirus disease 2019   Pandemic  

摘要： Background Neurology residents are particularly vulnerable to burnout because of the novel logistical and clinical challenges brought about by the coronavirus disease 2019 (COVID-19) pandemic. Despite its implications, knowledge on burnout and its predictors among neurology residents is lacking. This study aimed to determine the prevalence of burnout among neurology residents during the pandemic, to compare burnout subscale scores and sociodemographic and work characteristics, and to explore residents' perceptions on how to address burnout. Methods We conducted a cross-sectional survey among all 120 residents from the nine institutions in the Philippines offering neurology residency programs from March to August 2020. We obtained sociodemographic and work characteristics using questionnaire. We measured burnout using the Maslach Burnout Inventory. We performed an inductive thematic analysis to analyze perceptions on how to reduce burnout. Results The response rate was 71.67% (86/120). The mean age was 30.1 +/- 3.1 years. Using predefined subscale critical boundaries, the prevalence of burnout was 94% (95% CI 89, 99). The lack of compensation and number of on-duty days influenced emotional exhaustion scores. The number of on-duty days influenced depersonalization scores. Thematic analysis revealed five themes: increasing manpower;self-care;reducing clerical tasks;improving work environment;and adequate compensation. Conclusions The prevalence of burnout among neurology residents during the COVID-19 pandemic was alarmingly high. Reforms in hiring policies, work-hour management, manpower organization, work environment, and logistics may be considered.