Raiders of the CNS: New insights on microglia and myeloid infiltrates in EAE

Ilia Davidovich Vainchtein

    Research output: ThesisThesis fully internal (DIV)

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    Abstract

    Multiple Sclerosis (MS) is a central nervous system (CNS) disorder characterized by the loss of white matter, myelin, around the nerve cells and leads to e.g. paralysis of muscles. Usually the disorder starts with periods of paralysis and recoveries also known as the relapsing-remitting (RRMS) phase and develops into secondary progressive MS (SPSM), a phase with progressive decline without recovery. The immune system of the body is involved in MS, especially in RRMS, but the role of microglia, the local immune cells of the CNS, is unclear and often interpreted as disease supportive. In this dissertation a mouse model for MS, experimental autoimmune encephalomyelitis (EAE), is used to further understand the role of microglia. The results indicate that microglia take up very little myelin and are not disease supportive at the early phases of EAE. Their numbers increase, they develop more processes and take up dead or dying cells from their environment that also include infiltrated body immune cells. During remissions or at the later chronic phase, there are very few infiltrated body immune cells present in the CNS. At these stages microglia form nodules, clusters that are also found in SPSM, and have become very sensitive for inflammation inducing stimuli in their environment. These drastic changes in microglia might be important for the propagation of neurological damage upon EAE/SPMS when very few “damaging” body immune infiltrates are present but the disorder progresses. This shows that microglia might be interesting therapeutic targets for MS.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Boddeke, Erik, Supervisor
    • Eggen, Bart, Co-supervisor
    • Hintzen, R. Q., Assessment committee, External person
    • Kremer, Berry, Assessment committee
    • Owens, T., Assessment committee, External person
    Award date6-Sep-2016
    Place of Publication[Groningen]
    Publisher
    Print ISBNs978‐90‐367‐8995‐0
    Electronic ISBNs978‐90‐367‐8994‐3
    Publication statusPublished - 2016

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