B cells in central nervous system disease: diversity, locations and pathophysiology.
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ABSTRACT:
SUBMITTER: Jain RW
PROVIDER: S-EPMC8667979 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The transcriptional responses of cryptococcus during human infection are dynamic and highly dependent on the immediate signals from the environment. We examined the RNA-Seq profiles of Cryptococcus isoalted from human CSF and in comparison with to the same isolate's response to the stresses of artificial CSF and within the rabbit subarachnoid space as well as growth in nutritious media with little or no stress. By comparing these transcriptomes, we have identified regulated genes and categorized them by networks and functional classifications to identify candidate genes essential for yeast survival and as well as those uniformly expressed in CSF across diverse isolates that may be markers for the human disease state.
2021-03-30 | GSE171092 | GEO
Project description:IntroductionChronic progressive neuroinflammation is a hallmark of neurological lysosomal storage diseases, including mucopolysaccharidosis III (MPS III or Sanfilippo disease). Since neuroinflammation is linked to white matter tract pathology, we analyzed axonal myelination and white matter density in the mouse model of MPS IIIC HgsnatP304L and post-mortem brain samples of MPS III patients.MethodsBrain and spinal cord tissues of human MPS III patients, 6-month-old HgsnatP304L mice and age- and sex-matching wild type mice were analyzed by immunofluorescence to assess levels of myelin-associated proteins, primary and secondary storage materials, and levels of microgliosis. Corpus callosum (CC) region was studied by transmission electron microscopy to analyze axon myelination and morphology of oligodendrocytes and microglia. Mouse brains were analyzed ex vivo by high-filed MRI using Diffusion Basis Spectrum Imaging in Python-Diffusion tensor imaging algorithms.ResultsAnalyses of CC and spinal cord tissues by immunohistochemistry revealed substantially reduced levels of myelin-associated proteins including Myelin Basic Protein, Myelin Associated Glycoprotein, and Myelin Oligodendrocyte Glycoprotein. Furthermore, ultrastructural analyses revealed disruption of myelin sheath organization and reduced myelin thickness in the brains of MPS IIIC mice and human MPS IIIC patients compared to healthy controls. Oligodendrocytes (OLs) in the CC of MPS IIIC mice were scarce, while examination of the remaining cells revealed numerous enlarged lysosomes containing heparan sulfate, GM3 ganglioside or "zebra bodies" consistent with accumulation of lipids and myelin fragments. In addition, OLs contained swollen mitochondria with largely dissolved cristae, resembling those previously identified in the dysfunctional neurons of MPS IIIC mice. Ex vivo Diffusion Basis Spectrum Imaging revealed compelling signs of demyelination (26% increase in radial diffusivity) and tissue loss (76% increase in hindered diffusivity) in CC of MPS IIIC mice.DiscussionOur findings demonstrate an important role for white matter injury in the pathophysiology of MPS III. This study also defines specific parameters and brain regions for MRI analysis and suggests that it may become a crucial non-invasive method to evaluate disease progression and therapeutic response.
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Project description:ObjectivesTo identify and analyze the characteristics of the most influential articles about central nervous system (CNS) inflammatory demyelinating disease.Materials and methodsThe Institute for Scientific Information (ISI) Web of Science database and the 2014 Journal Citation Reports Science Edition were used to retrieve the top 100 cited articles on CNS inflammatory demyelinating disease. The citation numbers, journals, years of publication, authorships, article types, subjects and main issues were analyzed. For neuromyelitis optica (NMO), articles that were cited more than 100 times were regarded as a citation classic and described separately.ResultsThe top 100 cited articles were published between 1972 and 2011 in 13 journals. The highest number of articles (n = 24) was published in Brain, followed by The New England Journal of Medicine (n = 21). The average number of citations was 664 (range 330-3,897), and 64% of the articles were from the United States and the United Kingdom. The majority of the top 100 cited articles were related to multiple sclerosis (n = 87), and only a few articles reported on other topics such as NMO (n = 9), acute disseminated encephalomyelitis (n = 2) and optic neuritis (n = 2). Among the top 100 cited articles, 77% were original articles. Forty-one citation classics were found for NMO.ConclusionsOur study provides a historical perspective on the research progress on CNS inflammatory demyelinating disease and may serve as a guide for important advances and trends in the field for associated researchers.
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Project description:Coxsackievirus B (CVB) is a significant pathogen that causes pediatric central nervous system disease with acute syndromes commonly. The onset of its infection was abrupt, and after recovery there usually will be severe mental sequelae. The disease model for research was not established by the way of natural infection, although there are various investigations about the CVB-induced central nervous system (CNS) diseases. Thus, we have established an acute neonatal CNS disease mice model by CVB orally infecting. This model imitated the natural infection route and focuses the onset of CNS disease, inducing severe infection and lesion in the hippocampus and cortex regions, and the stability of the model was demonstrated. A pathology score system was developed for quantitative pathology analysis, which standardizes the CNS pathology analysis by statistics analysis. By this model, the track of CVB penetrating the blood brain barrier in vivo has been captured. One of the experimental strains CVB3/Macocy, as a new variant, was isolated, and its genomic RNA was cloned. According to its nucleotide sequence, we have characterized its genomic structure and defined its genotype. Based on the sequence, some mutations which do not change the CVB-induced CNS damage have been found. The model is an effective tool for studies on CVB-induced CNS diseases.
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Project description:Microglia serve as brain-resident myeloid cells that affect cerebral development, ischemia, neurodegeneration, and neuro-viral infection. MicroRNAs play a key role in central nervous system disease through post-transcriptional regulation. Indeed, evidence shows that microRNAs are one of the most important regulators mediating microglial activation, polarization, and autophagy, and subsequently affecting neuroinflammation and the outcome of central nervous system disease. In this review, we provide insight into the function of microRNAs, which may be an attractive strategy and influential treatment for microglia-related central nervous system dysfunction. Moreover, we comprehensively describe how microglia fight against central nervous system disease via multiple functional microRNAs.
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Project description:Urinary biomarkers can diagnose and monitor pathophysiologic conditions in the central nervous system (CNS). However, focus is often on single diseases, with limited data on discriminatory capability of this approach in a general setting. Here, we demonstrate that different classes of CNS disease exhibit distinct biomarker patterns, evidence of disease-specific "fingerprinting." Urine from 218 patients with pathology-confirmed tumors or cerebrovascular disease, controls (n = 33) were collected. ELISA and/or bead-based multiplexing quantified levels of 21 putative urinary biomarkers. Analysis identified biomarkers capable of distinguishing each disease from controls and other diseases. Mann-Whitney U tests identified biomarkers with differential expression between disease types and controls (P ≤ 0.001). Subsequent receiver-operating characteristic (ROC) analyses revealed distinguishing biomarkers with high sensitivity and specificity. Areas under the curve (AUCs) ranged 0.8563-1.000 (P values ≤ 0.0003), sensitivities ranged 80.00-100.00%, and specificities ranged 80.95-100.00%. These data demonstrate proof-of-principle evidence that disease-specific urinary biomarker signatures exist. In contrast to non-specific responses to ischemia or injury, these results suggest that urinary biomarkers accurately reflect unique biological processes distinct to different diseases. This work can be used to generate disease-specific panels for enhancing diagnosis, assisting less-invasive follow-up and herald utility by revealing putative disease-specific therapeutic targets.
| S-EPMC10630515 | biostudies-literature
Project description:The brown ghost knifefish (Apteronotus leptorhynchus) is a weakly electric teleost fish of particular interest as a model organism for a variety of research areas in neuroscience, including neurophysiology, neuroethology, and neurobiology. This versatile model system has been more recently used in the study of central nervous system development and regeneration during adulthood, as well as in the study of vertebrate aging and senescence. Despite substantial scientific interest in this species, no genomic resources are currently available. After evaluating several trimming and transcript reconstruction strategies, de novo assembly using Trinity uncovered at least 11,847 unique components (“genes”) containing full or near-full length protein sequences based on alignment to a reference set of known Actinopterygii protein sequences, with as many as 42,459 components containing at least a partial protein-coding sequence, providing broad coverage of the proteome. Shotgun proteomics confirmed translation of open reading frames from over 2,000 transcripts, including alternative splice variants. Assignment of tandem mass spectra obtained was shown to be greatly improved with the assembly compared with using databases of sequences from closely related organisms.
2015-07-16 | PXD001285 | Pride
Project description:Purpose of reviewCentral nervous system (CNS) tuberculosis is the most devastating form of tuberculosis (TB), with mortality and or neurological sequelae in over half of individuals. We reviewed original research and systematic reviews published since 1 January 2019 for new developments in CNS TB pathophysiology, diagnosis, management and prognosis.Recent findingsInsight in the pathophysiology is increasing steadily since the landmark studies in 1933, focussing on granuloma type classification, the relevance of the M. tuberculosis bacterial burden and the wide range of immunological responses. Although Xpert/RIF has been recommended by the WHO for extrapulmonary TB diagnosis, culture is still needed to increase the sensitivity of TB meningitis diagnosis. Sequential MRIs can improve understanding of neurological deficits at baseline and during treatment. Pharmacokinetic/pharmacodynamic modelling suggests that higher doses of rifampicin and isoniazid in TB meningitis could improve survival.SummaryRecent studies in the field of CNS-TB have largely focussed on TB meningitis. The outcome may improve by optimizing treatment dosing. This needs to be confirmed in clinical trials. Due to the important role of inflammation, these trials should be used as the platform to study the inflammatory and metabolomic responses. This could improve understanding of the biology of this disease and improve patient outlook by enabling individualised host-directed therapy.
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Project description:The tolerance of normal brain tissues limits the radiation dose that can be delivered safely during cranial radiotherapy, and one of the potential complications that can arise involves cognitive impairment. Extensive laboratory data have appeared recently showing that hippocampal neurogenesis is significantly impacted by irradiation and that such changes are associated with altered cognitive function and involve, in part, changes in the microenvironment (oxidative stress and inflammation). Although there is considerable uncertainty about exactly how these changes evolve, new in vitro and in vivo approaches have provided a means by which new mechanistic insights can be gained relevant to the topic. Together, the data from cell culture and animal-based studies provide complementary information relevant to a potentially serious complication of cranial radiotherapy and should enhance our understanding of the tolerance of normal brain after cranial irradiation.
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Project description:Rapid nerve conduction in the CNS is facilitated by the insulation of axons with myelin, a specialized oligodendroglial compartment distant from the cell body. Myelin is turned over and adapted throughout life; however, the molecular and cellular basis of myelin dynamics is not well understood. Hypothesizing that only a fraction of all myelin-related mRNAs has been identified so far, we subjected myelin biochemically purified from mouse brains at various ages to RNA sequencing. We find a surprisingly large pool of transcripts abundant and/or enriched in myelin. Furthermore, a comprehensive analysis showed that the myelin transcriptome is closely related to the myelin proteome but clearly distinct from the transcriptomes of oligodendrocytes and brain tissues, suggesting that the incorporation of mRNAs into the myelin compartment is highly selective. The mRNA-pool in myelin displays maturation-dependent dynamic changes of composition, abundance, and functional associations; however ageing-dependent changes after 6 months of age were minor. We suggest that this transcript pool provides a basis for the local modulation of myelin turnover and adaptation, i.e. in the individual internode. A light-weight membrane fraction enriched for myelin was purified from mouse brains as described previously (Jahn et al., Neuromethods, 2013). For RNA-Seq, RNA was isolated from myelin of mice from indicated ages.
2016-06-24 | E-GEOD-78151 | biostudies-arrayexpress