Aluminium in Brain Tissue in Multiple Sclerosis.
Ontology highlight
ABSTRACT:
SUBMITTER: Mold M
PROVIDER: S-EPMC6121957 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:MS is a primary demyelinating disease of the central nervous system. The cause is unknown and pathological hallmarks include plaque formation with immune cell infiltration. A microarray analysis of characterized brain tissue samples from three MS cases and a non-neurological control sample was performed containing over 22,000 genes. Real-time PCR analyses of 7 MS samples and 3 non-neurological control brain samples confirmed changes in expression in the chosen genes of interest. Experiment Overall Design: Three MS cases and a non-neurological control sample were used.
2008-06-14 | E-GEOD-5839 | biostudies-arrayexpress
Project description:(1) Introduction: Human exposure to aluminium is a burgeoning problem. In 1988, the population of the Cornish town of Camelford was exposed to exceedingly high levels of aluminium in their potable water supply. Herein we provide evidence that aluminium played a role in the death of a Camelford resident following development of late-onset epilepsy. (2) Case summary: We have measured the aluminium content of brain tissue in this individual and demonstrated significant accumulations of aluminium in the hippocampus (4.35 (2.80) µg/g dry wt.) and the occipital lobe (2.22 (2.23) µg/g dry wt., mean, SD, n = 5), the latter being associated with abnormal calcifications. Aluminium-specific fluorescence microscopy confirmed the presence of aluminium in both of these tissues and made the consistent observation of aluminium-loaded glial cells in close proximity to aluminium-rich cell/neuronal debris. These observations support an inflammatory component in this case of late-onset epilepsy. Congo red failed to identify any amyloid deposits in any tissue while thioflavin S showed extensive extracellular and intracellular tau pathologies. (3) Discussion: We present the first data showing aluminium in brain tissue in epilepsy and suggest, in light of complementary evidence from scientific literature, the first evidence that aluminium played a role in the advent of this case of late-onset adult epilepsy.
| S-EPMC6616903 | biostudies-literature
Project description:ObjectiveMultiple sclerosis (MS) is a common demyelinating central nervous system disease. MRI methods that can quantify myelin loss are needed for trials of putative remyelinating agents. Quantitative magnetization transfer MRI introduced the macromolecule proton fraction (MPF), which correlates with myelin concentration. We developed an alternative approach, Simultaneous-Multi-Angular-Relaxometry-of-Tissue (SMART) MRI, to generate MPF. Our objective was to test SMART-derived MPF metric as a potential imaging biomarker of demyelination.MethodsTwenty healthy control (HC), 11 relapsing-remitting MS (RRMS), 22 progressive MS (PMS), and one subject with a biopsied tumefactive demyelinating lesion were scanned at 3T using SMART MRI. SMART-derived MPF metric was determined in normal-appearing cortical gray matter (NAGM), normal-appearing subcortical white matter (NAWM), and demyelinating lesions. MPF metric was evaluated for correlations with physical and cognitive test scores. Comparisons were made between HC and MS and between MS subtypes. Furthermore, correlations were determined between MPF and neuropathology in the biopsied person.ResultsSMART-derived MPF in NAGM and NAWM were lower in MS than HC (p < 0.001). MPF in NAGM, NAWM and lesions differentiated RRMS from PMS (p < 0.01, p < 0.001, p < 0.001, respectively), whereas lesion volumes did not. MPF in NAGM, NAWM and lesions correlated with the Expanded Disability Status Scale (p < 0.01, p < 0.001, p < 0.001, respectively) and nine-hole peg test (p < 0.001, p < 0.001, p < 0.01, respectively). MPF was lower in the histopathologically confirmed inflammatory demyelinating lesion than the contralateral NAWM and increased in the biopsied lesion over time, mirroring improved clinical performance.InterpretationSMART-derived MPF metric holds potential as a quantitative imaging biomarker of demyelination and remyelination.
| S-EPMC9539387 | biostudies-literature
Project description:Multiple sclerosis (MS) is a neuroinflammatory disease characterized by loss of myelin (demyelination) and, to a certain extent, subsequent myelin repair (remyelination). To better understand the pathomechanisms underlying de- and remyelination and to monitor the efficacy of treatments aimed at regenerating myelin, techniques offering noninvasive visualizations of myelin are warranted. Magnetic resonance (MR) imaging has long been at the forefront of efforts to visualize myelin, but it has only recently become feasible to access the rapidly decaying resonance signals stemming from the myelin lipid-protein bilayer itself. Here, we show that direct MR mapping of the bilayer yields highly specific myelin maps in brain tissue from patients with MS. Furthermore, examination of the bilayer signal behavior is found to reveal pathological alterations in normal-appearing white and gray matter. These results indicate promise for in vivo implementations of the myelin bilayer mapping technique, with prospective applications in basic research, diagnostics, disease monitoring, and drug development.
| S-EPMC10421026 | biostudies-literature
Project description:Neuroinflammatory processes occurring during multiple sclerosis cause disseminated softening of brain tissue, as quantified by in vivo magnetic resonance elastography (MRE). However, inflammation-mediated tissue alterations underlying the mechanical integrity of the brain remain unclear. We previously showed that blood-brain barrier (BBB) disruption visualized by MRI using gadolinium-based contrast agent (GBCA) does not correlate with tissue softening in active experimental autoimmune encephalomyelitis (EAE). However, it is unknown how confined BBB changes and other inflammatory processes may determine local elasticity changes. Therefore, we aim to elucidate which inflammatory hallmarks are determinant for local viscoelastic changes observed in EAE brains. Hence, novel multifrequency MRE was applied in combination with GBCA-based MRI or very small superparamagnetic iron oxide particles (VSOPs) in female SJL mice with induced adoptive transfer EAE (n = 21). VSOPs were doped with europium (Eu-VSOPs) to facilitate the post-mortem analysis. Accumulation of Eu-VSOPs, which was previously demonstrated to be sensitive to immune cell infiltration and ECM remodeling, was also found to be independent of GBCA enhancement. Following registration to a reference brain atlas, viscoelastic properties of the whole brain and areas visualized by either Gd or VSOP were quantified. MRE revealed marked disseminated softening across the whole brain in mice with established EAE (baseline: 3.1 ± 0.1 m/s vs. EAE: 2.9 ± 0.2 m/s, p < 0.0001). A similar degree of softening was observed in sites of GBCA enhancement i.e., mainly within cerebral cortex and brain stem (baseline: 3.3 ± 0.4 m/s vs. EAE: 3.0 ± 0.5 m/s, p = 0.018). However, locations in which only Eu-VSOP accumulated, mainly in fiber tracts (baseline: 3.0 ± 0.4 m/s vs. EAE: 2.6 ± 0.5 m/s, p = 0.023), softening was more pronounced when compared to non-hypointense areas (percent change of stiffness for Eu-VSOP accumulation: -16.81 ± 16.49% vs. for non-hypointense regions: -5.85 ± 3.81%, p = 0.048). Our findings suggest that multifrequency MRE is sensitive to differentiate between local inflammatory processes with a strong immune cell infiltrate that lead to VSOP accumulation, from disseminated inflammation and BBB leakage visualized by GBCA. These pathological events visualized by Eu-VSOP MRI and MRE may include gliosis, macrophage infiltration, alterations of endothelial matrix components, and/or extracellular matrix remodeling. MRE may therefore represent a promising imaging tool for non-invasive clinical assessment of different pathological aspects of neuroinflammation.
| S-EPMC8419310 | biostudies-literature
Project description:Introduction: Multiple sclerosis (MS) is a chronic disorder of the central nervous system with an untreatable late progressive phase. Molecular maps of different stages of brain lesion evolution in patients with progressive multiple sclerosis (PMS) are missing but critical for understanding disease development and to identify novel targets to halt progression. Materials and Methods: The MS Atlas database comprises comprehensive high-quality transcriptomic profiles of 98 white matter (WM) brain samples of different lesion types (normal-appearing WM [NAWM], active, chronic active, inactive, remyelinating) from ten progressive MS patients and 25 WM areas from five non-neurological diseased cases. Results: We introduce the first MS brain lesion atlas (msatlas.dk), developed to address the current challenges of understanding mechanisms driving the fate on a lesion basis. The MS Atlas gives means for testing research hypotheses, validating biomarkers and drug targets. It comes with a user-friendly web interface, and it fosters bioinformatic methods for de novo network enrichment to extract mechanistic markers for specific lesion types and pathway-based lesion type comparison. We describe examples of how the MS Atlas can be used to extract systems medicine signatures and demonstrate the interface of MS Atlas. Conclusion: This compendium of mechanistic PMS WM lesion profiles is an invaluable resource to fuel future MS research and a new basis for treatment development.
| S-EPMC7500075 | biostudies-literature
Project description:Elevated genetic risk for multiple sclerosis originated in Steppe Pastoralist populations
| PRJEB65098 | ENA
Project description:Multiple sclerosis (MS) is an inflammatory demyelinating and degenerative disease of the central nervous system (CNS). Although inflammatory responses are efficiently treated, therapies for progression are scarce and suboptimal, and biomarkers to predict the disease course are insufficient. Cure or preventive measures for MS require knowledge of core pathological events at the site of the tissue damage. Novelties in systems biology have emerged and paved the way for a more fine-grained understanding of key pathological pathways within the CNS, but they have also raised questions still without answers. Here, we systemically review the power of tissue and single-cell/nucleus CNS omics and discuss major gaps of integration into the clinical practice. Systemic search identified 49 transcriptome and 11 proteome studies of the CNS from 1997 till October 2021. Pioneering molecular discoveries indicate that MS affects the whole brain and all resident cell types. Despite inconsistency of results, studies imply increase in transcripts/proteins of semaphorins, heat shock proteins, myelin proteins, apolipoproteins and HLAs. Different lesions are characterized by distinct astrocytic and microglial polarization, altered oligodendrogenesis, and changes in specific neuronal subtypes. In all white matter lesion types, CXCL12, SCD, CD163 are highly expressed, and STAT6- and TGFβ-signaling are increased. In the grey matter lesions, TNF-signaling seems to drive cell death, and especially CUX2-expressing neurons may be susceptible to neurodegeneration. The vast heterogeneity at both cellular and lesional levels may underlie the clinical heterogeneity of MS, and it may be more complex than the current disease phenotyping in the clinical practice. Systems biology has not solved the mystery of MS, but it has discovered multiple molecules and networks potentially contributing to the pathogenesis. However, these results are mostly descriptive; focused functional studies of the molecular changes may open up for a better interpretation. Guidelines for acceptable quality or awareness of results from low quality data, and standardized computational and biological pipelines may help to overcome limited tissue availability and the "snap shot" problem of omics. These may help in identifying core pathological events and point in directions for focus in clinical prevention.
| S-EPMC8924618 | biostudies-literature
Project description:Recent studies of cortical pathology in secondary progressive multiple sclerosis have shown that a more severe clinical course and the presence of extended subpial grey matter lesions with significant neuronal/glial loss and microglial activation are associated with meningeal inflammation, including the presence of lymphoid-like structures in the subarachnoid space in a proportion of cases. To investigate the molecular consequences of pro-inflammatory and cytotoxic molecules diffusing from the meninges into the underlying grey matter, we carried out gene expression profiling analysis of the motor cortex from 20 post-mortem multiple sclerosis brains with and without substantial meningeal inflammation and 10 non-neurological controls. Gene expression profiling of grey matter lesions and normal appearing grey matter not only confirmed the substantial pathological cell changes, which were greatest in multiple sclerosis cases with increased meningeal inflammation, but also demonstrated the upregulation of multiple genes/pathways associated with the inflammatory response. In particular, genes involved in tumour necrosis factor (TNF) signalling were significantly deregulated in MS cases compared to controls.
2019-12-17 | GSE135511 | GEO
Project description:HIV-Associated Neurocognitive Disorders (HAND) is a common manifestation of HIV infection that afflicts about 50 % of HIV-positive individuals. As people with access to antiretroviral treatments live longer, HAND can be found in increasing segments of populations at risk for other chronic, neurodegenerative conditions such as Alzheimer's disease (AD) and Multiple Sclerosis (MS). If brain diseases of diverse etiologies utilize similar biological pathways in the brain, they may coexist in a patient and possibly exacerbate neuropathogenesis and morbidity. To test this proposition, we conducted comparative meta-analysis of selected publicly available microarray datasets from brain tissues of patients with HAND, AD, and MS. In pair-wise and three-way analyses, we found a large number of dysregulated genes and biological processes common to either HAND and AD or HAND and MS, or to all three diseases. The common characteristic of all three diseases was up-regulation of broadly ranging immune responses in the brain. In addition, HAND and AD share down-modulation of processes involved, among others, in synaptic transmission and cell-cell signaling while HAND and MS share defective processes of neurogenesis and calcium/calmodulin-dependent protein kinase activity. Our approach could provide insight into the identification of common disease mechanisms and better intervention strategies for complex neurocognitive disorders.
| S-EPMC3515772 | biostudies-literature