scholarly journals The Distribution of GPR17-Expressing Cells Correlates with White Matter Inflammation Status in Brain Tissues of Multiple Sclerosis Patients

2021 ◽  
Vol 22 (9) ◽  
pp. 4574
Author(s):  
Jacopo Angelini ◽  
Davide Marangon ◽  
Stefano Raffaele ◽  
Davide Lecca ◽  
Maria P. Abbracchio
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Hla Antigen ◽  
Animal Models Of Disease ◽  
Control Subjects ◽  
Normal Appearing White Matter ◽  
Oligodendrocyte Precursor ◽  
Models Of Disease ◽  
Multiple Sclerosis Patients ◽  
And Control

In multiple sclerosis (MS), oligodendrocyte precursor cells (OPCs) are recruited to the site of injury to remyelinate damaged axons; however, in patients this process is often ineffective due to defects in OPC maturation. The membrane receptor GPR17 timely regulates the early stages of OPC differentiation; however, after reaching its highest levels in immature oligodendrocytes, it has to be downregulated to allow terminal maturation. Since, in several animal models of disease GPR17 is upregulated, the aim of this work was to characterize GPR17 alterations in MS patients. We developed immunohistochemistry and immunofluorescence procedures for the detection of GPR17 in human tissues and stained post-mortem MS brain lesions from patients with secondary progressive MS and control subjects. The inflammatory activity in each lesion was evaluated by immunohistochemistry for the myelin protein MOG and the HLA antigen to classify them as active, chronic inactive or chronic active. Hence, we assessed the distribution of GPR17-positive cells in these lesions compared to normal appearing white matter (NAWM) and white matter (WM) of control subjects. Our data have shown a marked increase of GPR17-expressing oligodendroglial cells accumulating at NAWM, in which moderate inflammation was also found. Furthermore, we identified two distinct subpopulations of GPR17-expressing oligodendroglial cells, characterized by either ramified or rounded morphology, that differently populate the WM of healthy controls and MS patients. We concluded that the coordinated presence of GPR17 in OPCs at the lesion sites and inflamed NAWM areas suggests that GPR17 could be exploited to support endogenous remyelination through advanced pharmacological approaches.

Low level of systemic autoimmunity in Western Australian multiple sclerosis patients

2010 ◽  
Vol 16 (3) ◽  
pp. 351-354 ◽  
Author(s):  
Wei Qiu ◽  
Christine Bundell ◽  
Jing-Shan Wu ◽  
Alison Castley ◽  
Ian James ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Antinuclear Antibody ◽  
Aquaporin 4 ◽  
Low Level ◽  
Control Subjects ◽  
Systemic Autoimmunity ◽  
Multiple Sclerosis Patients ◽  
And Control ◽  
Western Australian

Previous autoantibody (AAb) studies in multiple sclerosis MS have produced conflicting results. The objective of this study was to determine AAb frequency and association with the HLA-DRB1 genotype. Antinuclear antibody, antithyroid peroxidase and anti-aquaporin-4 assays and HLA-DRB1 genotyping were performed in 198 MS patients and 188 controls. There were no significant differences in AAb frequency or titres between MS and control subjects. AQP4-IgG was not found in any MS patients. There was no correlation between AAbs and HLA-DRB1 alleles. In conclusion, this study failed to confirm previous reports of increased AAbs in MS or to show an association between HLA-DRB1 genotype and the presence of AAbs.

scholarly journals Two Classes of T1 Hypointense Lesions in Multiple Sclerosis With Different Clinical Relevance

2021 ◽  
Vol 12 ◽  
Author(s):  
Krisztián Kocsis ◽  
Nikoletta Szabó ◽  
Eszter Tóth ◽  
András Király ◽  
Péter Faragó ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Black Holes ◽  
White Matter ◽  
Clinical Relevance ◽  
Spin Echo ◽  
Normal Appearing White Matter ◽  
Disability Status ◽  
Multiple Sclerosis Patients ◽  
Normal White Matter

Background: Hypointense lesions on T1-weighted images have important clinical relevance in multiple sclerosis patients. Traditionally, spin-echo (SE) sequences are used to assess these lesions (termed black holes), but Fast Spoiled Gradient-Echo (FSPGR) sequences provide an excellent alternative.Objective: To determine whether the contrast difference between T1 hypointense lesions and the surrounding normal white matter is similar on the two sequences, whether different lesion types could be identified, and whether the clinical relevance of these lesions types are different.Methods: Seventy-nine multiple sclerosis patients' lesions were manually segmented, then registered to T1 sequences. Median intensity values of lesions were identified on all sequences, then K-means clustering was applied to assess whether distinct clusters of lesions can be defined based on intensity values on SE, FSPGR, and FLAIR sequences. The standardized intensity of the lesions in each cluster was compared to the intensity of the normal appearing white matter in order to see if lesions stand out from the white matter on a given sequence.Results: 100% of lesions on FSPGR images and 69% on SE sequence in cluster #1 exceeded a standardized lesion distance of Z = 2.3 (p < 0.05). In cluster #2, 78.7% of lesions on FSPGR and only 17.7% of lesions on SE sequence were above this cutoff value, meaning that these lesions were not easily seen on SE images. Lesion count in the second cluster (lesions less identifiable on SE) significantly correlated with the Expanded Disability Status Scale (EDSS) (R: 0.30, p ≤ 0.006) and with disease duration (R: 0.33, p ≤ 0.002).Conclusion: We showed that black holes can be separated into two distinct clusters based on their intensity values on various sequences, only one of which is related to clinical parameters. This emphasizes the joint role of FSPGR and SE sequences in the monitoring of MS patients and provides insight into the role of black holes in MS.

scholarly journals Correction: Increased Perfusion in Normal Appearing White Matter in High Inflammatory Multiple Sclerosis Patients

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0142464 ◽  
Author(s):  
Maxim Bester ◽  
Nils Daniel Forkert ◽  
Jan Patrick Stellmann ◽  
Klarissa Stürner ◽  
Lilian Aly ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Normal Appearing White Matter ◽  
Multiple Sclerosis Patients

scholarly journals Increased Perfusion in Normal Appearing White Matter in High Inflammatory Multiple Sclerosis Patients

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0119356 ◽  
Author(s):  
Maxim Bester ◽  
Nils Daniel Forkert ◽  
Jan Patrick Stellmann ◽  
Lilian Aly ◽  
Anna Drabik ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Normal Appearing White Matter ◽  
Multiple Sclerosis Patients

scholarly journals Astrocyte metabolism in multiple sclerosis investigated by 1-C-11 acetate PET

2020 ◽  
pp. 0271678X2091146 ◽  
Author(s):  
Hiroki Kato ◽  
Tatsusada Okuno ◽  
Kayako Isohashi ◽  
Toru Koda ◽  
Mikito Shimizu ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
White Matter ◽  
Fractional Anisotropy ◽  
Normal Control ◽  
Gray Matter ◽  
Control Subjects ◽  
Quantitative Pet ◽  
Fiber Tracts ◽  
Positron Emission ◽  
Multiple Sclerosis Patients

This study was aimed at evaluating the metabolism of reactive astrocytes in the brains of patients with multiple sclerosis by quantitative 1-C-11 acetate positron emission tomography (PET). Magnetic resonance imaging and 1-C-11 quantitative PET were performed in eight patients with multiple sclerosis and 10 normal control subjects. The efflux rate (k2) of 1-C-11 acetate, which reportedly reflects the metabolic rate of 1-C-11 acetate, was calculated based on the one-tissue compartmental model. Fractional anisotropy was also determined to evaluate the integrity of the neuronal tracts. The values of k2 in the patients with multiple sclerosis were significantly higher than those in the normal control subjects, in both the white matter ( p = 0.003) and the gray matter ( p = 0.02). In addition, the white matter/gray matter ratio of k2 was significantly higher in the multiple sclerosis patients than in the normal control subjects ( p = 0.02). Voxel-based statistical analysis revealed most prominent increase in k2 in the neuronal fiber tracts, as well as decrease in fractional anisotropy in them in the multiple sclerosis patients. The present study clarified that the pathological changes associated with astrocytic reactivation in multiple sclerosis patients could be visualized by quantitative 1-C-11 acetate PET.

Sign in / Sign up

Export Citation Format

Share Document