关键词： Emergency medical services   Out-of-hospital cardiac arrest   Blood gases   Hydrogen-ion concentration  

摘要： BackgroundThe knowledge of new prognostic factors in out-of-hospital cardiac arrest (OHCA) that can be evaluated since the beginning of cardiopulmonary resuscitation (CPR) manoeuvres could be helpful in the decision-making process of prehospital care. We aim to identify metabolic variables at the start of advanced CPR at the scene that may be associated with two main outcomes of CPR (recovery of spontaneous circulation (ROSC) and neurological outcome).MethodsProspective observational study of all non-traumatic OHCA in patients older than 17years assisted by emergency medical services (EMS), with doctor and nurse on board, between January 2012 and December 2017. Venous blood gases were sampled upon initially obtaining venous access to determine the initial values of pH, pCO(2), HCO3-, base excess (BE), Na+, K+, Ca2+ and lactate. ROSC upon arrival at the hospital and neurological status 30days later (Cerebral Performance Categories (CPC) scale) were *** included 1552 patients with OHCA with blood test data in a 6-year period. ROSC was achieved in 906 cases (58.4%), and good neurological recovery at 30days (CPC I-II) occurred in 383 cases (24.68%). In multivariate analysis, we found a significant relationship between non-recovery of spontaneous circulation (no-ROSC) and low pH levels (adjusted odds ratio (OR) 0.03 (0.002-0.59), p=0.020), high pCO(2) levels (adjusted OR 1.03 [1.01-1.05], p=0.008) and high potassium levels (adjusted OR 2.28 [1.43-3.61], p=0.008). Poor neurological outcomes were associated with low pH levels (adjusted OR 0.06 [0.02-0.18], p<0.001), high pCO(2) (adjusted OR 1.05 [1.03-1.08], p<0.001), low HCO3- (adjusted OR 0.97 [0.94-0.999], p=0.044), low BE (adjusted OR 0.96 [0.93-0.98], p<0.001) and high potassium levels (adjusted OR 1.37 [1.16-1.60], p<0.001).ConclusionThere is a significant relationship between severe alterations of venous blood-gas variables and potassium at the start of CPR of non-traumatic OHCA and low-ROSC rate and

关键词： Glycyrrhizin   HMGB1   pharmacological inhibitor   neuroprotection   neurological disorders   inflammation  

摘要： Glycyrrhizin (glycyrrhizic acid), a bioactive triterpenoid saponin constituent of Glycyrrhiza glabra, is a traditional medicine possessing a plethora of pharmacological anti-inflammatory, antioxidant, antimicrobial, and antiaging properties. It is a known pharmacological inhibitor of high mobility group box 1 (HMGB1), a ubiquitous protein with proinflammatory cytokinelike activity. HMGB1 has been implicated in an array of inflammatory diseases when released extracellularly, mainly by activating intracellular signaling upon binding to the receptor for advanced glycation end products (RAGE) and toll-like receptor 4 (TLR4). HMGB1 neutralization strategies have demonstrated disease-modifying outcomes in several preclinical models of neurological disorders. Herein, we reveal the potential neuroprotective effects of glycyrrhizin against several neurological disorders. Emerging findings demonstrate the therapeutic potential of glycyrrhizin against several HMGB1-mediated pathological conditions including traumatic brain injury, neuroinflammation and associated conditions, epileptic seizures, Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Glycyrrhizin's effects in neurological disorders are mainly attributed to the attenuation of neuronal damage by inhibiting HMGB1 expression and translocation as well as by downregulating the expression of inflammatory cytokines. A large number of preclinical findings supports the notion that glycyrrhizin might be a promising therapeutic alternative to overcome the shortcomings of the mainstream therapeutic strategies against neurological disorders, mainly by halting disease progression. However, future research is warranted for a deeper exploration of the precise underlying molecular mechanism as well as for clinical translation.

关键词： Immunohistochemistry techniques   Immunostaining   Cerebellum   Neurons   Thalamus   Cerebral cortex   Central nervous system   Cytoplasm  

摘要： Genetically modified swine disease models are becoming increasingly important for studying molecular, physiological and pathological characteristics of human disorders. Given the limited history of these model systems, there remains a great need for proven molecular reagents in swine tissue. Here, to provide a resource for neurological models of disease, we validated antibodies by immunohistochemistry for use in examining central nervous system (CNS) markers in a recently developed miniswine model of neurofibromatosis type 1 (NF1). NF1 is an autosomal dominant tumor predisposition disorder stemming from mutations in NF1, a gene that encodes the Ras-GTPase activating protein neurofibromin. Patients classically present with benign neurofibromas throughout their bodies and can also present with neurological associated symptoms such as chronic pain, cognitive impairment, and behavioral abnormalities. As validated antibodies for immunohistochemistry applications are particularly difficult to find for swine models of neurological disease, we present immunostaining validation of antibodies implicated in glial inflammation (CD68), oligodendrocyte development (NG2, O4 and Olig2), and neuron differentiation and neurotransmission (doublecortin, GAD67, and tyrosine hydroxylase) by examining cellular localization and brain region specificity. Additionally, we confirm the utility of anti-GFAP, anti-Iba1, and anti-MBP antibodies, previously validated in swine, by testing their immunoreactivity across multiple brain regions in mutant NF1 samples. These immunostaining protocols for CNS markers provide a useful resource to the scientific community, furthering the utility of genetically modified miniswine for translational and clinical applications.

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.