关键词： Dendritic cells   Drug delivery systems   Neurological disorders   Dendritic cell-targeted therapies   Disease-specific therapies  

摘要： Dendritic cells (DCs) are the immune system's highly specialized antigen-presenting cells. When DCs are sluggish and mature, self-antigen presentation results in tolerance;however, when pathogen-associated molecular patterns stimulate mature DCs, antigen presentation results in the development of antigen-specific immunity. DCs have been identified in various vital organs of mammals (e.g., the skin, heart, lungs, intestines, and spleen), but the brain has long been thought to be devoid of DCs in the absence of neuroinflammation. However, neuroinflammation is becoming more recognized as a factor in a variety of brain illnesses. DCs are present in the brain parenchyma in trace amounts under healthy circumstances, but their numbers rise during neuroinflammation. New therapeutics are being developed that can reduce dendritic cell immunogenicity by inhibiting pro-inflammatory cytokine production and T cell co-stimulatory pathways. Additionally, innovative ways of regulating dendritic cell growth and differentiation and harnessing their tolerogenic capability are being explored. Herein, we described the function of dendritic cells in neurological disorders and discussed the potential for future therapeutic techniques that target dendritic cells and dendritic cell-related targets in the treatment of neurological disorders.

关键词： Neurology   Neuroradiology   Neurosurgery   Psychiatry  

关键词： Mitochondrial DNA   Immune response   Central nervous system   Gut microbiome   SARS-CoV-2   COVID-19  

摘要： Mitochondrial DNA (mtDNA) heteroplasmy is the dynamically determined co-expression of wild type (WT) inherited polymorphisms and collective time-dependent somatic mutations within individual mtDNA genomes. The temporal expression and distribution of cell-specific and tissue-specific mtDNA heteroplasmy in healthy individuals may be functionally associated with intracellular mitochondrial signaling pathways and nuclear DNA gene expression. The maintenance of endogenously regulated tissue-specific copy numbers of heteroplasmic mtDNA may represent a sensitive biomarker of homeostasis of mitochondrial dynamics, metabolic integrity, and immune competence. Myeloid cells, monocytes, macrophages, and antigen-presenting dendritic cells undergo programmed changes in mitochondrial metabolism according to innate and adaptive immunological processes. In the central nervous system (CNS), the polarization of activated microglial cells is dependent on strategically programmed changes in mitochondrial function. Therefore, variations in heteroplasmic mtDNA copy numbers may have functional consequences in metabolically competent mitochondria in innate and adaptive immune processes involving the CNS. Recently, altered mitochondrial function has been demonstrated in the progression of coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Accordingly, our review is organized to present convergent lines of empirical evidence that potentially link expression of mtDNA heteroplasmy by functionally interactive CNS cell types to the extent and severity of acute and chronic post-COVID-19 neurological disorders.

关键词： AAV9   cisterna magna   gene therapy   neurological disorders  

关键词： Neurology   Outcomes research   Biomedicine   general   Neurosciences   Anatomy   Human Physiology   Neurochemistry   Neuropsychology  

摘要： Study design Retrospective review of ISNCSCI datasets. Objectives To discuss the correct classification of ISNCSCI datasets considered as challenging. Setting International expert collaboration. Methods The International Standards Committee of the American Spinal Injury Association (ASIA) receives challenging case scenarios regarding the International Standards for the Neurological Classification of Spinal Cord Injury (ISNCSCI). Among those cases received, sample cases representing different categories of typical classification difficulties were identified by members of the International Standards committee. Results From the cases received, five sample cases were identified as representative for publication. These cases are related to the correct classification in the presence of non-SCI related conditions, the determination of motor zones of partial preservation in regions with no myotomes to test, the classification of the ASIA Impairment Scale in patients with substantial motor function below the motor level but no sacral sparing, the inclusion of non-key muscle functions in the classification of sensory incomplete individuals, and the correct classification of individuals with an amputation. Conclusion Presenting cases with challenging classifications, along with responses and explanations, will serve spinal cord injury professionals to better understand and utilize the ISNCSCI classification. As the ISNCSCI endorsed by ASIA and the International Spinal Cord Society (ISCoS) evolves over time, such resources are important to clarify inquiries from the spinal cord injury community and to understand the rationale for revisions.

关键词： MALDI IMS   Spatial distributions   Molecular map   Mass spectrometry   Brain disease   Neurology   Histology  

摘要： Neurological disease and disorders remain a large public health threat. Thus, research to improve early detection and/or develop more effective treatment approaches are necessary. Although there are many common techniques and imaging modalities utilized to study these diseases, existing approaches often require a label which can be costly and time consuming. Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) is a label-free, innovative and emerging technique that produces 2D ion density maps representing the distribution of an analyte(s) across a tissue section in relation to tissue histopathology. One main advantage of MALDI IMS over other imaging modalities is its ability to determine the spatial distribution of hundreds of analytes within a single imaging run, without the need for a label or any a priori knowledge. Within the field of neurology and disease there have been several impactful studies in which MALDI IMS has been utilized to better understand the cellular pathology of the disease and or severity. Furthermore, MALDI IMS has made it possible to map specific classes of analytes to regions of the brain that otherwise may have been lost using more traditional methods. This review will highlight key studies that demonstrate the potential of this technology to elucidate previously unknown phenomenon in neurological disease.

关键词： Diseases of the nervous system   Spinal cord diseases   Biomedicine   general   Neurosciences   Anatomy   Human Physiology   Neurochemistry   Neuropsychology  

摘要： Study design Retrospective cohort study. Objectives To evaluate the effects of older age at the time of injury on the individuals' survival and neurological recovery within the first year after acute traumatic spinal cord injury (tSCI). Setting United States. Methods This study included all participants enrolled into the First National Acute Spinal Cord Injury Study (NASCIS-1). Outcome measures included survival and neurological recovery (as assessed using the NASCIS motor and sensory scores) within the first year after tSCI. Data analyses of neurological recovery were adjusted for major potential confounders. Results The study included 39 females and 267 males with overall mean age of 31 years who mostly sustained cervical severe tSCI after motor vehicle accidents or falls. Survival rates among older individuals are significantly lower than among younger individuals within the first year following tSCI (p < 0.0001). Among who survived the first year of tSCI, there were no statistically significant difference between older survivors and younger survivors regarding motor and sensory recovery in the multiple regression analyses adjusted for major potential confounders. Conclusions The results of this retrospective study suggest that older age at the injury onset is associated with lower survival rate within the first year following tSCI. However, older individuals have similar potential to recover from their initial neurological impairment to younger individuals after tSCI. The results of this study combined to the recent literature underline the need for multidisciplinary team approach to the management of the elderly with acute SCI is essential to maximize their recovery.

关键词： Cerebrovascular disease   Dilatative arteriopathy   MMP inhibition   Neurodegenerative diseases   Neuroprotection  

摘要： Matrix metalloproteinases (MMPs) are a group of endopeptidases that degrade the extracellular matrix and are responsible for many physiological and pathological processes. We aim to review the MMP inhibition from a clinical perspective and its possible therapeutic use in the future. MMPs play a role in various neurodegenerative and cerebrovascular diseases such as large artery atherosclerosis and ischemic stroke;for example, MMPs increase blood-brain barrier permeability favoring neuroinflammation. Synthetic MMPs inhibitors have been tested mostly in oncological trials and failed to demonstrate efficacy;some of them were discontinued because of the severe adverse reactions. Tetracyclines, in submicrobial doses, act as an MMP inhibitor, although tetracyclines have not yet been proven effective in several neurological conditions in which they were tested against placebo;it is uncertain whether there may be a use for tetracyclines in cerebrovascular disease, as a neuroprotective agent or in dolichoectasia.

关键词： Methodology   Behavioural neurology   Multiverse   Open science   Stroke  

摘要： Objective Multiverse analysis provides an ideal tool for understanding how inherent, yet ultimately arbitrary methodological choices impact the conclusions of individual studies. With this investigation, we aimed to demonstrate the utility of multiverse analysis for evaluating generalisability and identifying potential sources of bias within studies employing neurological populations. Methods Multiverse analysis was used to evaluate the robustness of the relationship between post-stroke visuospatial neglect and poor long-term recovery outcome within a sample of 1113 (age = 72.5, 45.1% female) stroke survivors. A total of 25,600 t-test comparisons were run across 400 different patient groups defined using various combinations of valid inclusion criteria based on lesion location, stroke type, assessment time, neglect impairment definition, and scoring criteria across 16 standardised outcome measures. Results Overall, 33.9% of conducted comparisons yielded significant results. 99.9% of these significant results fell below the null specification curve, indicating a highly robust relationship between neglect and poor recovery outcome. However, the strength of this effect was not constant across all comparison groups. Comparisons which included < 100 participants, pre-selected patients based on lesion type, or failed to account for allocentric neglect impairment were found to yield average effect sizes which differed substantially. Similarly, average effect sizes differed across various outcome measures with the strongest average effect in comparisons involving an activities of daily living measure and the weakest in comparisons employing a depression subscale. Conclusions This investigation demonstrates the utility of multiverse analysis techniques for evaluating effect robustness and identifying potential sources of bias within neurological research.

关键词： Neurological services   COVID-19   Neurology   Health services administration   Policies  

摘要： Background The COVID-19 pandemic outbreak has dramatically disrupted healthcare systems. Two rapid WHO pulse surveys studied disruptions in mental health services, but did not particularly focus on neurology. Here, a global survey was conducted and addresses the impact of the pandemic on neurology services. Methods A cross-sectional study was carried out in which 34 international neurological associations were asked to distribute the survey to national associations. The responses represented the national situation, in November-December 2020, with regard to the main disrupted neurological services, reasons and the mitigation strategies implemented as well as the disruption on training of residents and on neurological research. A comparison with the situation in February-April 2020, first pandemic wave, was also requested. Findings 54 completed surveys came from 43 countries covering all the 6 WHO regions. Overall, neurological services disruption was reported as mild by 26%, moderate by 30%, complete by 13% of associations. The most affected services were cross-sectoral neurological services (57%) and neurorehabilitation (56%). The second wave of the pandemic, however, was associated with the improvement of service provision for diagnostics services (44%) and for neurorehabilitation (41%). Governmental directives were the major cause of services' disruption (56%). Mitigation strategies were mostly established through telemedicine (48%). Almost half of respondents reported a significant impact on neurological research (48%) and educational activities (60%). Most associations (67%) were not involved in decision making for neurological patients' issues by their national government. Interpretation The COVID-19 pandemic affects neurological services and raises the universal need for the development of neurological health care at the policy, systems and services levels. A global national plan on mitigation strategies for disruption of neurological services during pandemic