关键词： Germinal matrix hemorrhage   Innate immunity   Hematoma resolution   Inflammation  

摘要： Germinal matrix hemorrhage is induced by stereotaxic injection of collagenase into the germinal matrix of P7 Sprague-Dawley rats. Hemoglobin assay, western blot, immunofluorescence and neurobehavioral tests were used to test the effects of BLVRA on hematoma resolution and anti-inflammatory response. We showed that BLVRA triggered a signaling cascade that ameliorated post-hemorrhagic neurological deficits in both short-term and long-term neurobehavioral tests in a GMH rat model. Specifically, BLVRA inhibited toll-like receptor 4 (TLR4) expression by translocating to the nucleus in an endothelial nitric oxide (eNOS)/nitric oxide (NO)-dependent manner. BLVRA also induced the upregulation of CD36 scavenger receptor level in microglia/microphages, of which the prominent role is to enhance hematoma resolution. However, the beneficial effects of BLVRA were abolished with the knockdown of eNOS, indicating that the eNOS/NO system is an important downstream factor of BLVRA. Our results demonstrate a mechanism of BLVRA modulating hematoma resolution and suppressing inflammation through eNOS/NO/TLR4 pathway in the GMH rat model.

关键词： Biomarker   Brain injury   Neurologic injury   Critical illness   Pediatric  

摘要： Unexpected neurological morbidity in Pediatric Intensive Care Units (PICUs) remains high and is difficult to detect proactively. Brain-specific biomarkers represent a novel approach for early detection of neurological injury. We sought to determine whether serum concentrations of neuron-specific enolase (NSE), myelin basic protein (MBP), and S100B, specific for neurons, oligodendrocytes, and glia, respectively, were predictive of neurological morbidity in critically ill children. Serum was prospectively collected on days 1-7 from diagnostically diverse PICU patients (n = 103). Unfavorable neurological outcome at hospital discharge was defined as Pediatric Cerebral Performance Category (PCPC) score of 3-6 with a deterioration from baseline. NSE, MBP, and S100B concentrations were measured by enzyme-linked immunosorbent assay. Peak biomarker levels were greater in patients with unfavorable versus favorable neurological outcome [NSE 39.4 +/- 44.1 vs. 12.2 +/- 22.9 ng/ml (P = 0.005), MBP 9.1 +/- 11.5 vs. 0.6 +/- 1.3 ng/ml (P = 0.003), S100B 130 +/- 232 vs. 34 +/- 70 pg/ml (P = 0.04), respectively;mean +/- SD]. Peak levels were each independently associated with unfavorable neurological outcome when controlling for presence of primary neurologic admission diagnosis and poor baseline PCPC using logistic regression analysis (NSE, P = 0.04;MBP, P = 0.004;S100B, P = 0.04), and had the following receiver operating characteristics: NSE 0.75 (0.58, 0.92), MBP 0.81 (0.66, 0.94), and S100B 0.80 (0.67, 0.93) (area under the curve [95% confidence intervals]). Prospectively collected brain-specific serum biomarkers predict unfavorable neurological outcome in critically ill children. Serum biomarkers used in conjunction with clinical data could be used to generate models predicting early detection of neurological injury, allowing for more timely diagnostic and therapeutic interventions, potentially reducing neurological morbidity in the PICU.

关键词： Ginger   6-gingerol   6-shogaol   Zingerone   Age-related neurological disorders  

摘要： Age-related neurological disorders (ANDs), including neurodegenerative diseases, are multifactorial disorders with a risk that increases with aging. ANDs are generally characterized by common neuropathological conditions of the central nervous system, such as oxidative stress, neuroinflammation, and protein misfolding. Recently, efforts have been made to overcome ANDs because of the increase in age-dependent prevalence. Ginger, the rhizome of Zingiber officinale Roscoe, is a popular food spice and has a long history of use in traditional medicine for treating various disease symptoms. The structure-activity relationships of ginger phytochemicals show that ginger can be used to treat ANDs by targeting different ligand sites. This review shows that ginger and its constituents, such as 6-gingerol, 6-shogaol, 6-paradol, zingerone, and dehydrozingerone, are effective for ameliorating the neurological symptoms and pathological conditions of ANDs through by modulating cell death or cell survival signaling molecules. From this review, we conclude that the active ingredients in ginger have therapeutic potential in ANDs.

关键词： Schizophrenia   Psychosis   Psychopathology   Neurological signs  

摘要： Neurological soft signs (NSS) are one of the biomarkers for schizophrenia spectrum disorders. However, a few studies have examined the prevalence of NSS across the schizophrenia spectrum. The present study adopted a quasi-longitudinal study design and examined the prevalence of NSS and their associations with clinical and behavioural manifestations in participants in different stages of the illness. The abridged version of the Cambridge Neurological Inventory was administered to 39 patients with the first-episode schizophrenia, 39 individuals with ultra-high risk (UHR) for psychosis, 39 individuals with schizotypy, and 39 healthy controls. Patients with the first-episode schizophrenia had a higher prevalence of NSS in motor coordination than healthy controls as well as individuals with UHR and schizotypy. Individuals with UHR exhibited a higher prevalence of sensory integration items than individuals with schizotypy and healthy controls. Discriminant analysis classified the membership of the individuals correctly across the spectrum with an accuracy of up to 60.9%. In particular, NSS could discriminate individuals with UHR from healthy controls at up to 85.9% accuracy. These findings suggest that NSS are robust biomarkers to detect and discriminate individuals in different stages of the schizophrenia spectrum from healthy controls.

关键词： Acquired hepatocerebral degeneration   Hepatic encephalopathy   Cirrhosis   Manganese   Portosystemic shunts   Liver transplant  

摘要： We discuss the case of a rare and often unrecognized neurologic syndrome, called Acquired Hepatocerebral Degeneration (AHD), observed in patients with advanced liver disease and portosystemic shunts. The clinical manifestations can be very heterogeneous and in our case included a combination of cerebellar and extrapyramidal signs, arisen in a period of few days. Brain Magnetic Resonance Imaging (MRI) showed, in T1-weighted images, diffuse bilateral hyper intensities in basal ganglia and biemispheric brain and cerebellar cortices, resembling paramagnetic deposits. No other neurological impairments, like stroke, infection or neoplasia, were found. It was excluded an episode of acute hepatic encephalopathy. We also ruled out Wilsonian degeneration, iron overload and autoimmune encephalitis and we lastly found high manganese levels as the possible cause of the brain paramagnetic deposits. Even though either serum Mn determination or its accumulation in the brain are not specific for AHD, however the chronic and progressively worsening of the neurological manifestations advocated a degenerative condition, possibly AHD. We finally opted for the early restoration of liver function by OLT, and we observed complete clinical symptoms' resolution and partial MRI reversal after a follow up of 6 months.

关键词： Preterm   Magnetic resonance imaging   Neuromotor   Neurological   Neurobehaviour  

摘要： Aim: This study aimed to examine associations between structural MRI and concurrent motor, neurological and neurobehavioral measures at 30-32 weeks postmenstrual age (PMA;'Early'), and at term equivalent age ('Term'). Method: In this prospective cohort study, infants underwent Early MRI (n = 119;73 male;median 32 weeks 1 day PMA) and Term MRI (n = 102;61 male;median 40 weeks 4 days PMA) at 3 T. Structural images were scored generating white matter (WM), cortical gray matter, deep gray matter, cerebellar and global brain abnormality scores. Clinical measures were General Movements Assessment (GMs), Hammersmith Neonatal Neurological Examination (HNNE) and NICU Neonatal Neurobehavioral Scale (NNNS). The Premie-Neuro was administered Early and the Test of Infant Motor Performance (TIMP) and a visual assessment at Term. Results: Early MRI cerebellar scores were strongly associated with neurological components of HNNE (reflexes), NNNS (Hypertonicity), the Premie-Neuro neurological subscale (regression coefficient beta = -0.06;95% confidence interval CI = -0.09, -0.04;p <.001) and cramped-synchronized GMs (beta = 1.10;95%CI = 0.57, 1.63;p <.001). Term MRI WM and global scores were strongly associated with the TIMP (WM beta = -1.02;95%CI = -1.67, -0.36;p =.002;global beta = -1.59;95%CI = -2.62, -0.56;p =.001). Interpretation: Brain structure on Early and Term MRI was associated with concurrent motor, neurological and neurobehavioral function in very preterm infants.

关键词： Disc injury   Posterior ligamentous complex injury   Thoracolumbar burst fractures  

摘要： Objective: To formulate radiological indexes based on CT for further MRI examination to detect posterior ligamentous complex injury (PLC) or disc injury in thoracolumbar burst fractures without neurological deficit in the emergent setting. Materials and methods: Patients with a single thoracolumbar burst fracture and no neurological deficit were included into this study. Radiological indexes on CT included canal compromise (CC), anterior and posterior vertebral height ratio (PVH and AVH ratio), local kyphosis (LK) and regional kyphosis (RK). PLC and disc injury were assessed on MRI. Statistical analysis was performed to identify the predictive power for radiological indexes for any MRI findings either or both disc and PLC injury. Results: Eighty-four patients were included in this study. According to MRI, patients with no PLC and disc injury were allocated into MRI finding negative group, others were defined as positive group. There was no significant difference in AVH ratio, PVH ratio and RK between these two groups. The CC and LK were significant higher in positive group than that in negative group (p < 0.001). The areas under receiver operating characteristic curve were 0.826 and 0.893 for CC and LK respectively and without significant difference. The best thresholds for CC and LK were 0.19 (sensitivity: 69.4%;specificity: 87.5%) and 14.00 degrees (sensitivity: 83.3%;specificity: 83.3%), respectively. Conclusion: The presence of CC > 0.19 and/or LK > 14.00 degrees on CT scan can predict MRI findings including PLC and disc injury. These thresholds may be the guideline for MRI examination in patients with neurologically intact thoracolumbar burst fracture in the emergent condition. (C) 2017 Elsevier Ltd. All rights reserved.

摘要： Functional Neurological Symptom Disorder (FND) is a relatively common neurological condition, accounting for approximately 3-6% of neurologist referrals. FND is considered a transient disorder of neuronal function, sometimes linked to physical trauma and psychological stress. Despite this, chronic disability is common, for example, around 40% of adults with motor FND have permanent disability. Building on current theoretical models, this paper proposes that microglial dysfunction could perpetuate functional changes within acute motor FND, thus providing a pathophysiological mechanism underlying the chronic stage of the motor FND phenotypes seen clinically. Core to our argument is microglia's dual role in modulating neuroimmunity and their control of synaptic plasticity, which places them at a pathophysiological nexus wherein coincident physical trauma and psychological stress could cause long-term change in neuronal networks without producing macroscopic structural abnormality. This model proposes a range of hypotheses that are testable with current technologies.

关键词： NITRONES   PYRAZINES   BRAIN-derived neurotrophic factor   CYCLIC nucleotides   PHOSPHODIESTERASES  

摘要： BACKGROUND AND PURPOSE Neuronal regeneration from endogenous precursors is an attractive strategy for the treatment of ischaemic stroke. However, most stroke-generated newborn neurons die over time. Therefore, a drug that is both neuroprotective and pro-neurogenic may be beneficial after stroke. Here, we assessed the neurogenic and oligodendrogenic effects of tetramethylpyrazine nitrone (TBN), a neuroprotective drug candidate for stroke, in a rat model of ischaemic stroke. EXPERIMENTAL APPROACH We used Sprague Dawley rats with middle cerebral artery occlusion (MCAO). TBN was administered by tail vein injection beginning at 3h post ischaemia. Therapeutic effect of TBN was evaluated by neurological behaviour and cerebral infarction. Promotion of neurogenesis and oligodendrogenesis was determined by double immunofluorescent staining and Western blotting analyses. Primary cultures of cortical neurons were used to assess the effect of TBN on neuronal differentiation in vitro. KEY RESULTS TBN reduced cerebral infarction, preserved and/or restored neurological function and promoted neurogenesis and oligodendrogenesis in rats after MCAO. In addition, TBN stimulated neuronal differentiation on primary culture of cortical neurons in vitro. Pro-neurogenic effects of TBN were attributed to its activation of the AKT/cAMP responsive element-binding protein through increasing brain-derived neurotrophic factor (BDNF) expression, as shown by the abolition of the effects of TBN by a specific inhibitor of BDNF receptor ANA-12 and by the PI3K inhibitor LY294002. CONCLUSION AND IMPLICATIONS As TBN can simultaneously provide neuroprotection and pro-neurogenic effects, it may be a promising treatment for both acute phase neuroprotection and long-term functional recovery after ischaemic stroke.

关键词： Cohort study   Epidemiology   Human papillomavirus   Vaccine Safety  

摘要： BackgroundSince 2006, human papillomavirus (HPV) vaccines have been introduced in many countries worldwide. Whilst safety studies have been reassuring, focus has been on the primary target group, the young adolescent girls. However, it is also important to evaluate safety in adult women where background disease rates and safety issues could differ significantly. ObjectiveWe took advantage of the unique Danish and Swedish nationwide healthcare registers to conduct a cohort study comparing incidence rate ratios (RRs) of 45 preselected serious chronic diseases in quadrivalent HPV (qHPV)-vaccinated and qHPV-unvaccinated adult women 18-44years of age. MethodsWe used Poisson regression to estimate RRs according to qHPV vaccination status with two-sided 95% confidence intervals (95% CIs). ResultsThe study cohort comprised 3126790 women (1195865 [38%] Danish and 1930925 [62%] Swedish) followed for 16386459 person-years. Vaccine uptake of at least one dose of qHPV vaccine was 8% in the cohort: 18% amongst Danish women and 2% amongst Swedish. We identified seven adverse events with statistically significant increased risks following vaccinationHashimoto's thyroiditis, coeliac disease, localized lupus erythematosus, pemphigus vulgaris, Addison's disease, Raynaud's disease and other encephalitis, myelitis or encephalomyelitis. After taking multiple testing into account and conducting self-controlled case series analyses, coeliac disease (RR 1.56 [95% confidence interval 1.29-1.89]) was the only remaining association. ConclusionUnmasking of conditions at vaccination visits is a plausible explanation for the increased risk associated with qHPV in this study because coeliac disease is underdiagnosed in Scandinavian populations. In conclusion, our study of serious adverse event rates in qHPV-vaccinated and qHPV-unvaccinated adult women 18-44years of age did not raise any safety issues of concern.