关键词： Coronaviruses   COVID-19   SARS-CoV-2   Centralnervoussystem   Brain-lung-brainaxis  

摘要： Coronaviruses (CoVs) are large positive stranded enveloped RNA viruses that generally cause enteric and respiratory diseases in humans and in animals. Most human CoVs have recently attracted global attention to their lethal potential and great infectious capacity. A highly pathogenic CoV, called COVID-19 or SARS-CoV-2, dramatically emerged in December 2019 in Wuhan, China. This new CoV has caused severe pneumonia in China and rapidly spreads around the world, the COVID-19 pandemic. Growing evidence pieces show that viruses, such as CoVs, can enter the central nervous system from different pathways and inducing neurotoxicity. Therefore, it is urgent to make clear whether SARS-CoV-2 has access to the central nervous system and can cause direct neuronal effects. Moreover, a brain-lung-brain axis is been proposed from the scientific community where severe neurological dysfunction and injury are associated with lung injury, and vice versa. In this axis, virus-induced inflammation and oxidative stress could be the common mechanisms responsible for CoV neurological symptoms. Therefore, is important to make clear whether SARS-CoV-2 lung damage can cause direct or indirect neuronal effects. (C) 2020 Elsevier B.V. and Japan Neuroscience Society. All rights reserved.

关键词： cardiopulmonary bypass   cardiac arrest   resuscitation   rewarming  

摘要： The lowest recorded core temperature from which a person with accidental hypothermia has survived neurologically intact is 11.8 degrees C in a 2-y-old boy. The lowest recorded temperature from which an adult has been resuscitated neurologically intact is 13.7 degrees C in a 29-y-old woman. The lowest core temperature with survival from induced hypothermia has been quoted as 9 degrees C. We discovered a case series (n=50) from 1961 in which 5 patients with core temperatures below 11.8 degrees C survived neurologically intact. The lowest core temperature in this group was 4.2 degrees C. The authors also presented cardiovascular and other physiologic data at various core temperatures. The patients in the case series showed a wide variation in individual physiological responses to hypothermia. It is not known whether survival from accidental hypothermia is possible with a core temperature below 11.8 degrees C, but this case series suggests that the lower limit for successful resuscitation may be far lower. We advise against using core temperature alone to decide whether a hypothermic patient in cardiac arrest has a chance of survival.

关键词： Stem cell   Neurogenesis   Brain organoid   Disease modeling   Neurodevelopmental disease  

摘要： Stem cells are characterized by self-renewal and by their ability to differentiate into cells of various organs. With massive progress in 2D and 3D cell culture techniques, in vitro generation of various types of such organoids from patient-derived stem cells is now possible. As in vitro differentiation protocols are usually made to resemble human developmental processes, organogenesis of patient-derived stem cells can provide key information regarding a range of developmental diseases. Human stem cell-based in vitro modeling as opposed to using animal models can particularly benefit the evaluation of neurological diseases because of significant differences in structure and developmental processes between the human and the animal brain. This review focuses on stem cell-based in vitro modeling of neurodevelopmental disorders, more specifically, the fundamentals and technical advancements in monolayer neuron and brain organoid cultures. Furthermore, we discuss the drawbacks of the conventional culture method and explore the advanced, cutting edge 3D organoid models for several neurodevelopmental diseases, including genetic diseases such as Down syndrome, Rett syndrome, and Miller-Dieker syndrome, as well as brain malformations like macrocephaly and microcephaly. Finally, we discuss the limitations of the current organoid techniques and some potential solutions that pave the way for accurate modeling of neurological disorders in a dish.

关键词： Neurogenic   Urinary bladder   Pathophysiology   Proteomics   Neurotrophins  

摘要： Objectives The aim of this study was to investigate the disease-specific urinary levels variations of neurotrophins (NGF, BDNF), mediators of inflammation (TGF beta-1, PGE-2) and markers of extracellular matrix alterations (TIMP-2) in patients with multiple sclerosis (MS) spinal cord injury (SCI), or spina bifida (SB), and neurogenic detrusor overactivity (NDO). Methods A prospective single-center study was conducted between March 2015 and March 2017. Patients aged over 18 years old, with neurological disease, with a urodynamic diagnosis of NDO were included. The urinary levels of NGF, BDNF, TIMP-2, PGE 2, and TGF-beta 1 were measured using dedicated ELISA kits. Results Forty-one patients were included: 6 with MS, 20 with SCI, and 15 with spina bifida. The average urinary level of NGF/Cr was significantly higher in MS patients compared to other neurologic populations (8 vs. 0.56 vs. 1.25 pg/mg of creatinine;p = 0.001) as well for the average urinary level of BDNF (88.3 vs. 5 vs. 4.8 pg/mg of creatinine;p < 0.0001). SCI patients had a significantly lower level of TGF beta-1 than SB patients (p = 0.04). The urinary level of PGE2 was significantly correlated with the Body Mass Index (r = 0.61;p = 0.0002). Conclusion All NDO may not be created equal from the molecular standpoint. Multiple sclerosis patients had higher urinary levels of neurotrophins than in other neurologic populations with NDO. Urinary TGF beta-1, a strong determinant of extracellular matrix, was significantly higher in spina bifida patients compared to SCI patients. These findings underscore the importance of using and interpreting those possible urinary markers in a disease-specific fashion.

关键词： integrative medicine   complementary and alternative medicine   child neurology   pediatric neurology   resident education   medical education  

摘要： Pediatric neurology patients frequently use integrative medicine;however, providers may feel uncomfortable or unfamiliar with these therapies. Child neurologist attitudes toward integrative medicine and educational needs in integrative medicine have not been assessed. A national, anonymous survey was distributed to Child Neurology residents (n=294) and program directors (n=71) to assess attitudes toward specific integrative medicine modalities, practices in discussing integrative medicine with patients, and perceived need for a curriculum on integrative medicine;61 (17%) partially and 53 (15%) fully completed the survey. Comparative analyses applied chi-square and independent t tests. Qualitative content analysis was performed on free text responses. Most providers surveyed consider mind and body practices safe (93% of respondents) and effective (84%), but have concerns about the safety of chiropractic manipulation (56% felt this was harmful), and the efficacy of homeopathy (none considered this effective). Few inquire about patient integrative medicine use regularly. Child Neurology residents are interested in further education on this topic.

关键词： Cerebral hemorrhage   Rats   Polydatin   Nerve function   Nuclear factor related factor 2  

摘要： This study investigates the effect of polydatin on the neurological function of cerebral hemorrhage rats and on the Nrf2 pathway of the endogenous antioxidant system in tissues around cerebral hematoma. Further, the study also aims to provide solid insights for clinical diagnosis and treatment. A total of 54 SPF grade male Wistar rats were divided into three groups: the sham group, model group, and polydatin group. Various parameters such as neurological deficit score, brain water content, pathological morphology, oxidative stress index content, Nrf2, NQO1, HO-1 mRNA expression, and the expression of HO-1, Nrf2, and kelch-like epichlorohydrin-1 (Keap1) protein were observed. Compared with the sham group, the mNSS score and brain water content of rats in the model group increased significantly after dosing (P < 0.05). When compared with the model group, the mNSS score and brain water content of rats in the polydatin group decreased significantly after dosing (P < 0.05). Compared with the other group, the serum NSE content of rats in the polydatin group decreased (P < 0.05). An increase was observed in the contents of NO, SOD, MDA, GSSG, and GSH in the brain tissue of rats in the model group when compared with the sham group. Compared with the model group, the contents of NO and MDA in the brain tissue of rats in the polydatin group decreased, while the contents of SOD, GSSG, and GSH increased (P < 0.05). The relative expressions of Nrf2, NQO1, and HO-1mRNA in the brain tissue of rats in the polydatin group was relatively high compared with both groups (P < 0.05). Polydatin can improve the neurological function of ICH rats and reduce the oxidative stress response by regulating the Nrf2-ARE pathway and downstream gene expression. This study preliminarily discussed the relevant mechanism of polydatin in the treatment of ICH rats, thus providing a theoretical reference to ICH treatment.

关键词： stroke   neurological disease   cell therapy   stem cell   microglia   mononuclear cell   PBMC   pleiotropic effects   polarization  

摘要： Stroke remains a major cause of serious disability because the brain has a limited capacity to regenerate. In the last two decades, therapies for stroke have dramatically changed. However, half of the patients cannot achieve functional independence after treatment. Presently, cell-based therapies are being investigated to improve functional outcomes. This review aims to describe conventional cell therapies under clinical trial and outline the novel concept of polarized cell therapies based on protective cell phenotypes, which are currently in pre-clinical studies, to facilitate functional recovery after post-reperfusion treatment in patients with ischemic stroke. In particular, non-neuronal stem cells, such as bone marrow-derived mesenchymal stem/stromal cells and mononuclear cells, confer no risk of tumorigenesis and are safe because they do not induce rejection and allergy;they also pose no ethical issues. Therefore, recent studies have focused on them as a cell source for cell therapies. Some clinical trials have shown beneficial therapeutic effects of bone marrow-derived cells in this regard, whereas others have shown no such effects. Therefore, more clinical trials must be performed to reach a conclusion. Polarized microglia or peripheral blood mononuclear cells might provide promising therapeutic strategies after stroke because they have pleiotropic effects. In traumatic injuries and neurodegenerative diseases, astrocytes, neutrophils, and T cells were polarized to the protective phenotype in pre-clinical studies. As such, they might be useful therapeutic targets. Polarized cell therapies are gaining attention in the treatment of stroke and neurological diseases.

关键词： Cognitive behavior therapy   Online   Cognitive rehabilitation   Disability   Mental health   Neurological disorders  

摘要： Objective: Mental health and cognitive difficulties are highly prevalent across neurological disorders and significantly contribute to poorer patient outcomes. Unfortunately, access to effective psychological services for these comorbidities are limited. To determine whether a novel transdiagnostic internet-delivered psychological intervention, the Wellbeing Neuro Course, was feasible, acceptable and efficacious a single-group feasibility open trial was employed. Methods: The Wellbeing Neuro Course, targets mental health and cognitive difficulties, across a variety of neurological disorders. It is comprised of six online lessons, based on Cognitive Behavioural Therapy and Compensatory Cognitive Rehabilitation, delivered over 10 weeks and provided with weekly support from mental health professional via email and telephone. 105 adults with diagnoses of either epilepsy, multiple sclerosis, Parkinson's disease and/or acquired brain injury, underwent the intervention. Results: The intervention was found to be highly acceptable with high intervention completion and levels of satisfaction (> 95%). There was evidence of clinically significant improvements in primary outcomes (within group Cohen's d;average reductions) of depression (d = 0.93;avg. reduction >= 36%), anxiety (ds = 0.66, avg. reduction >= 36%), and disability (ds >= 0.49;avg. reduction >= 23%) at post-intervention, maintained at 3-month follow-up. For secondary outcomes there were significant improvements in fatigue severity and perceived cognitive difficulties of attention, planning and prospective memory. Findings were achieved with minimal clinician time, highlighting its public health potential. Conclusion: This open trial provides preliminary evidence the Wellbeing Neuro Course is acceptable and reduces symptoms of depression, anxiety and disability in neurological disorders. Future controlled trials of the intervention are now needed.