关键词： Herpes simplex virus   Next generation sequencing   Encephalitis   Steroid   The Gambia   Travel associated   Yellow fever vaccine associated neurological disease  

摘要： BackgroundHuman encephalitis can originate from a variety of different aetiologies, of which infection is the most common one. The diagnostic work-up is specifically challenging in patients with travel history since a broader spectrum of unfamiliar additional infectious agents, e. g. tropical disease pathogens, needs to be considered. Here we present a case of encephalitis of unclear aetiology in a female traveller returning from Africa, who in addition developed an atypical herpes simplex virus (HSV) encephalitis in close temporal relation with high-dose steroid *** presentationA previously healthy 48-year-old female presented with confusion syndrome and impaired vigilance which had developed during a six-day trip to The Gambia. The condition rapidly worsened to a comatose state. Extensive search for infectious agents including a variety of tropical disease pathogens was unsuccessful. As encephalitic signs persisted despite of calculated antimicrobial and antiviral therapy, high-dose corticosteroids were applied intravenously based on the working diagnosis of an autoimmune encephalitis. The treatment did, however, not improve the patient's condition. Four days later, bihemispheric signal amplification in the insular and frontobasal cortex was observed on magnetic resonance imaging (MRI). The intracranial pressure rapidly increased and could not be controlled by conservative treatment. The patient died due to tonsillar herniation 21days after onset of symptoms. Histological examination of postmortem brain tissue demonstrated a generalized lymphocytic meningoencephalitis. Immunohistochemical reactions against HSV-1/2 indicated an atypical manifestation of herpesviral encephalitis in brain tissue. Moreover, HSV-1 DNA was detected by a next-generation sequencing (NGS) metagenomics approach. Retrospective analysis of cerebrospinal fluid (CSF) and serum samples revealed HSV-1 DNA only in specimens one day ante *** case shows that standard hi

摘要： This special issue entitled "Mechanistic underpinnings of stem cell therapy for neurological disorders" brings together academicians, clinicians and industry partners with vested interest in the safe and effective translation of stem cell-based therapeutics from the laboratory to the clinic. Despite the scientific advances and limited clinical trials of stem cell therapy for neurological disorders, the mechanisms of action remain not fully understood. Here, we provide critical analyses of the therapeutic pathways postulated to mediate stem cell therapy. The views expressed here are based on scientific evidence, but also well-rationalized speculative hypotheses are encouraged in order to guide the field in exploiting the likely responsive pathways, as well as in exploring novel candidate targets which may open venues in optimizing the therapeutic effects of stem cell therapy. In the end, our goal is to coalesce the concerted efforts from stem cell researchers in probing the mechanistic triggers of cell-based treatments towards ensuring the safety and efficacy profiles of stem cell therapy.

关键词： Zika virus   Brain diseases   Infection   Outbreak   Brazil  

关键词： Childhood stroke   Treadmill exercise   Autophagy   HMGB1  

摘要： Aims: Treadmill exercise is a beneficial treatment following childhood stroke. Thus, studies focusing on the neuroprotective mechanism of exercise training during postischemic treatment in children with ischemic stroke are urgently needed. We evaluated the effects of treadmill exercise on autophagy after cerebral ischemia in young rats. Main methods: Rats (23-25 days old) underwent cerebral ischemia-reperfusion (CI/R) surgery. The experimental animals were divided into 5 groups, and some groups received either treadmill exercise, a rapamycin (RAPA) injection or combination therapy for 3 or 7 days. We performed a series of experimental tests including neurological scoring, hematoxylin-eosin staining (H&E), Nissl staining, triphenyl tetrazolium chloride (TTC) staining, Western blot analysis (WB), immunofluorescence (IF), enzyme-linked immunosorbent assay (ELISA), transmission electron microscopy (TEM) and Terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) fluorescence. Key findings: The experimental data indicated that treadmill exercise inhibited autophagy in the ischemic penumbra, inhibited high mobility group box 1 (HMGB1) translocation and binding to Beclin1, reduced apoptosis, reduced infarct volumes, and aided in functional recovery. However, RAPA promoted the opposite effects of treadmill exercise. Significance: We found that treadmill exercise improves the neurological deficits induced by CI/R by inhibiting autophagy and HMGB1 binding to Beclin1.

关键词： Cognitive ageing   Molecular medicine   Neuroscience   Proteomics  

摘要： Identifying biological correlates of late life cognitive function is important if we are to ascertain biomarkers for, and develop treatments to help reduce, age-related cognitive decline. Here, we investigated the associations between plasma levels of 90 neurology-related proteins (Olink (R) Proteomics) and general fluid cognitive ability in the Lothian Birth Cohort 1936 (LBC1936, N=798), Lothian Birth Cohort 1921 (LBC1921, N=165), and the INTERVAL BioResource (N=4451). In the LBC1936, 22 of the proteins were significantly associated with general fluid cognitive ability (beta between -0.11 and -0.17). MRI-assessed total brain volume partially mediated the association between 10 of these proteins and general fluid cognitive ability. In an age-matched subsample of INTERVAL, effect sizes for the 22 proteins, although smaller, were all in the same direction as in LBC1936. Plasma levels of a number of neurology-related proteins are associated with general fluid cognitive ability in later life, mediated by brain volume in some cases.

关键词： Primary measles encephalitis   Acute post-measles encephalitis   SSPE   MIBE   Measles immunization   Vaccine hesitancy  

摘要： Purpose of Review Owing to vaccine hesitancy, there has been a resurgence of measles infections in developed countries. Practitioners can expect to see an increase in patients with neurologic complications of measles. These devastating disorders include primary measles encephalitis, acute post measles encephalitis, subacute sclerosing panencephalitis (SSPE), and measles inclusion body encephalitis (MIBE). Recent Findings Although there are many unanswered questions regarding the neurologic complications of measles, recent advances have led to better understanding of the mechanism of the spread of measles within the nervous system, particularly the disruption of F protein function, which raises the possibility of treatment with fusion-inhibiting molecules. Measles and its neurological complications are preventable and must be prevented. Neurologists must educate other clinicians and the public regarding the consequences of inadequate herd immunity to measles. More effective treatments for SSPE and MIBE may be available in the near future, but currently these remain lethal diseases.

关键词： Gene therapy   gene delivery   neurological diseases   CRISPER   Cas9 system   viral vectors   non-viral vectors   Autism Spectrum disorder  

摘要： Major advancements in targeted gene therapy have opened up avenues for the treatment of major neurological disorders through a range of versatile modalities varying from expression of exogenous to suppression of endogenous genes. Recent technological innovations for improved gene sequence delivery have focussed on highly specific viral vector designs, plasmid transfection, nanoparticles, polymer-mediated gene delivery, engineered microRNA and in vivo clustered regulatory interspaced short palindromic repeats (CRISPR)-based therapeutics. These advanced techniques have profound applications in treating highly prevalent neurological diseases and neurodevelopmental disorders including Parkinson's disease, Alzheimer's disease and autism spectrum disorder, as well as rarer diseases such as amyotrophic lateral sclerosis (ALS), spinal muscular atrophy, lysosomal storage diseases, X-linked adrenoleukodystrophy and oncological diseases. In this article, we present an overview of the latest advances in targeted gene delivery and discuss the challenges and future direction of gene therapy in the treatment of neurological disorders.

关键词： Vesicles   X-rays   Lipids   Membranes   Mixtures  

摘要： Ethanolamine plasmalogen (EtnPLA) is a conical-shaped ether lipid and an essential component of neurological membranes. Low stability against oxidation limits its study in experiments. The concentration of EtnPLA in the bilayer varies depending on cell type and disease progression. Here we report on mixed bilayers of 1-palmitoy1-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-(1Z-octadecenyl)-2-oleoyl-sn-glycero-3-phosphoethanolamine (C18(Plasm)-18:1PE, PLAPE), an EtnPLA lipid subtype, at mole ratios of 2:1, 1:1, and 1:2. We present X-ray diffuse scattering (XDS) form factors F(q(z)) from oriented stacks of bilayers, related electron-density profiles, and hydrocarbon chain NMR order parameters. To aid future research on EtnPLA lipids and associated proteins, we have also extended the CHARMM36 all-atom force field to include the PLAPE lipid. The ability of the new force-field parameters to reproduce both X-ray and NMR structural properties of the mixed bilayer is remarkable. Our results indicate a thickening of the bilayer upon incorporation of increasing amounts of PLAPE into mixed bilayers, a reduction of lateral area per molecule, and an increase in lipid tail-ordering. The lateral compressibility modulus (K-A) calculated from simulations yielded values for PLAPE similar to POPC.

关键词： nervous system disorders   denmark   suicide  

摘要： This population epidemiology study uses Danish registry data to examine associations between neurological disorders and higher suicide rates from 1980 through 2016. Question Is there an association between neurological disorders and a higher risk of death by suicide? Findings In this retrospective cohort study that included 7300395 persons in Denmark from 1980 through 2016, there was a significantly higher rate of suicide among those with a diagnosed neurological disorder than all other persons (44.0 per 100000 person-years vs 20.1 per 100000 person-years, adjusted incidence rate ratio, 1.8). Meaning In Denmark, having a diagnosis of a neurological disorder was associated with a small but statistically significant increased risk of death by suicide. Importance Neurological disorders have been linked to suicide, but the risk across a broad spectrum of neurological disorders remains to be assessed. Objectives To examine whether people with neurological disorders die by suicide more often than other people and to assess for temporal associations. Design, Setting, and Participants Nationwide, retrospective cohort study on all persons 15 years or older living in Denmark, from 1980 through 2016 (N = 7300395). Exposures Medical contact for head injury, stroke, epilepsy, polyneuropathy, diseases of myoneural junction, Parkinson disease, multiple sclerosis, central nervous system infections, meningitis, encephalitis, amyotrophic lateral sclerosis, Huntington disease, dementia, intellectual disability, and other brain diseases from 1977 through 2016 (n = 1248252). Main Outcomes and Measures Death by suicide during 1980-2016. Adjusted incidence rate ratio (IRRs) were estimated using Poisson regressions, adjusted for sociodemographics, comorbidity, psychiatric diagnoses, and self-harm. Results Of the more than 7.3 million individuals observed over 161935233 person-years (49.1% males), 35483 died by suicide (median duration of follow-up, 23.6 years;interquartile range, 10.0-37.0