Sex, aging and immunity in multiple sclerosis and experimental autoimmune encephalomyelitis: An intriguing interaction

Boziki, Marina; Theotokis, Paschalis; Kesidou, Evangelia; Karafoulidou, Eleni; Konstantinou, Chrystalla; Michailidou, Iliana; Bahar, Yasemin; Altıntaş, Ayşe; Grigoriadis, Nikolaos

doi:10.3389/fneur.2022.1104552

Cited by 4 publications

(1 citation statement)

References 145 publications

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“…In recent years, age has been identified as a strong modulator of the MS phenotype. Increasing age in MS patients is associated with a reduced relapse rates and response to disease modifying therapies [ 4 , 14 , 16 , 17 ]. Interestingly, we identified age as the strongest factor modulating microglia numbers in our cohort of MS post-mortem tissue samples.…”

Section: Discussionmentioning

confidence: 99%

Microglia activation in periplaque white matter in multiple sclerosis depends on age and lesion type, but does not correlate with oligodendroglial loss

Kessler,

Thomas,

Kuhlmann

2023

Acta Neuropathol

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Multiple sclerosis (MS) is the most frequent inflammatory and demyelinating disease of the CNS. The disease course in MS is highly variable and driven by a combination of relapse-driven disease activity and relapse-independent disease progression. The formation of new focal demyelinating lesions is associated with clinical relapses; however, the pathological mechanisms driving disease progression are less well understood. Current concepts suggest that ongoing focal and diffuse inflammation within the CNS in combination with an age-associated failure of compensatory and repair mechanisms contribute to disease progression. The aim of our study was to characterize the diffuse microglia activation in periplaque white matter (PPWM) of MS patients, to identify factors modulating its extent and to determine its potential correlation with loss or preservation of oligodendrocytes. We analyzed microglial and oligodendroglial numbers in PPWM in a cohort of 96 tissue blocks from 32 MS patients containing 100 lesions as well as a control cohort (n = 37). Microglia activation in PPWM was dependent on patient age, proximity to lesion, lesion type, and to a lesser degree on sex. Oligodendrocyte numbers were decreased in PPWM; however, increased microglia densities did not correlate with lower oligodendroglial cell counts, indicating that diffuse microglia activation is not sufficient to drive oligodendroglial loss in PPWM. In summary, our findings support the notion of the close relationship between focal and diffuse inflammation in MS and that age is an important modulator of MS pathology.

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Section: Discussionmentioning

confidence: 99%

Microglia activation in periplaque white matter in multiple sclerosis depends on age and lesion type, but does not correlate with oligodendroglial loss

Kessler,

Thomas,

Kuhlmann

2023

Acta Neuropathol

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Active and non-active secondary progressive multiple sclerosis patients exhibit similar disability progression: results of an Italian MS registry study (ASPERA)

Chisari,

Amato,

Di Sapio

et al. 2024

J Neurol

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Abstract‘Active’ and ‘non-active’ secondary progressive MS (SPMS) have distinct pathophysiological mechanisms and clinical characteristics, but there is still no consensus regarding the frequency of these MS forms in the real-world setting. We aimed to evaluate the frequency of ‘active’ and ‘non-active’ SPMS in a large cohort of Italian MS patients and the differences in terms of clinical and MRI characteristics and disease progression. This multicenter study collected data about MS patients who have transitioned to the SP form in the period between 1st January 2014 and 31st December 2019 and followed by the MS centers contributing to the Italian MS Registry. Patients were divided into ‘active SPMS’ and ‘non-active SPMS’, based on both reported MRI data and relapse activity in the year before conversion to SPMS. Out of 68,621, 8,316 (12.1%) patients were diagnosed with SPMS. Out of them, 872 (10.5%) were classified into patients with either ‘active’ or ‘non-active’ SPMS. A total of 237 were classified into patients with ‘active SPMS’ (27.2%) and 635 as ‘non-active SPMS’ (72.8%). ‘Non-active SPMS’ patients were older, with a longer disease duration compared to those with ‘active SPMS’. The percentages of patients showing progression independent of relapse activity (PIRA) at 24 months were similar between ‘active’ and ‘non-active’ SPMS patients (67 [27.4%] vs 188 [29.6%]; p = 0.60). In the ‘active’ group, 36 (15.2%) patients showed relapse-associated worsening (RAW). Comparison of the survival curves to EDSS 6 and 7 according to disease activity did not show significant differences (p = 0.68 and p = 0.71). ‘Active’ and ‘non-active’ SPMS patients had a similar risk of achieving disability milestones, suggesting that progression is primarily attributed to PIRA and only to a small extent to disease activity.

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Unveiling the fate and potential neuroprotective role of neural stem/progenitor cells in multiple sclerosis

Hijal,

Fouani,

Awada

2024

Front. Neurol.

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Chronic pathological conditions often induce persistent systemic inflammation, contributing to neuroinflammatory diseases like Multiple Sclerosis (MS). MS is known for its autoimmune-mediated damage to myelin, axonal injury, and neuronal loss which drive disability accumulation and disease progression, often manifesting as cognitive impairments. Understanding the involvement of neural stem cells (NSCs) and neural progenitor cells (NPCs) in the remediation of MS through adult neurogenesis (ANG) and gliogenesis—the generation of new neurons and glial cells, respectively is of great importance. Hence, these phenomena, respectively, termed ANG and gliogenesis, involve significant structural and functional changes in neural networks. Thus, the proper integration of these newly generated cells into existing circuits is not only key to understanding the CNS’s development but also its remodeling in adulthood and recovery from diseases such as MS. Understanding how MS influences the fate of NSCs/NPCs and their possible neuroprotective role, provides insights into potential therapeutic interventions to alleviate the impact of MS on cognitive function and disease progression. This review explores MS, its pathogenesis, clinical manifestations, and its association with ANG and gliogenesis. It highlights the impact of altered NSCs and NPCs’ fate during MS and delves into the potential benefits of its modifications. It also evaluates treatment regimens that influence the fate of NSCS/NPCs to counteract the pathology subsequently.

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Sex, aging and immunity in multiple sclerosis and experimental autoimmune encephalomyelitis: An intriguing interaction

Cited by 4 publications

References 145 publications

Microglia activation in periplaque white matter in multiple sclerosis depends on age and lesion type, but does not correlate with oligodendroglial loss

Microglia activation in periplaque white matter in multiple sclerosis depends on age and lesion type, but does not correlate with oligodendroglial loss

Active and non-active secondary progressive multiple sclerosis patients exhibit similar disability progression: results of an Italian MS registry study (ASPERA)

Unveiling the fate and potential neuroprotective role of neural stem/progenitor cells in multiple sclerosis

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