University of Groningen. Raiders of the CNS Vainchtein, Ilia Davidovich

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1 University of Groningen Raiders of the CNS Vainchtein, Ilia Davidovich IMPORTANT NOTE: You are advised to consult the publisher's version (publisher's PDF) if you wish to cite from it. Please check the document version below. Document Version Publisher's PDF, also known as Version of record Publication date: 2016 Link to publication in University of Groningen/UMCG research database Citation for published version (APA): Vainchtein, I. D. (2016). Raiders of the CNS: New insights on microglia and myeloid infiltrates in EAE [Groningen]: Rijksuniversiteit Groningen Copyright Other than for strictly personal use, it is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), unless the work is under an open content license (like Creative Commons). Take-down policy If you believe that this document breaches copyright please contact us providing details, and we will remove access to the work immediately and investigate your claim. Downloaded from the University of Groningen/UMCG research database (Pure): For technical reasons the number of authors shown on this cover page is limited to 10 maximum. Download date:

2 Raiders of the CNS New insights on microglia and myeloid infiltrates in EAE Ilia D. Vainchtein

3 Most research described in this PhD dissertation was conducted at the Section Medical Physiology, Department of Neuroscience, University Medical Center Groningen, University of Groningen, The Netherlands. The research in this dissertation has been financially supported by the Dutch MS Research Foundation ( MS) and stichting Jan Kornelis de Cock. Printing of this dissertation was supported by: The Dutch MS Research Foundation University Medical Center Groningen University of Groningen Research School BCN Cover design: Ilia D. Vainchtein, Hilmar van Weering and Suping Peng. On the cover: The dim light and damaged wire are metaphors for the damage occurring in EAE. Print: Ipskamp Printing ISBN printed version: ISBN electronic version: Copyright 2016 by Ilia Davidovich Vainchtein. All rights reserved. No part of this thesis may be reproduced or transmitted in any form or by any means without prior permission of the author and the publishers holding the copyrights of the published articles.

4 Raiders of the CNS New insights on microglia and myeloid infiltrates in EAE Proefschrift ter verkrijging van de graad van doctor aan de Rijksuniversiteit Groningen op gezag van de rector magnificus prof. dr. E. Sterken en volgens besluit van het College voor Promoties. De openbare verdediging zal plaatsvinden op dinsdag 6 september 2016 om uur door Ilia Davidovich Vainchtein geboren op 12 juli 1988 te Kazan, Rusland

5 Promotor Prof. dr. H.W.G.M. Boddeke Copromotor Dr. B.J.L. Eggen Beoordelingscommissie Prof. dr. R.Q. Hintzen Prof. dr. H.P.H. Kremer Prof. dr. T. Owens

6 Paranimphs: Ming San Ma Nieske Brouwer

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8 Content Preface 9 Chapter 1 11 General introduction Chapter 2 37 In acute experimental autoimmune encephalomyelitis, invading macrophages are immune activated whereas microglia remain immune suppressed Chapter 3 61 Microglia are less pro inflammatory than myeloid infiltrates in the hippocampus of mice exposed to status epilepticus Chapter 4 87 Isolation of microglia and immune infiltrates from mouse and primate central nervous system Chapter Hyper ramified, hypersensitive microglia in a mouse model for Secondary Progressive Multiple Sclerosis Chapter MHCII pos microglia in chronic EAE phagocytose peripheral immune infiltrates Chapter Ly 6G pos CD11b low neutrophils are the main pro inflammatory myeloid infiltrates in EAE Chapter Summary and general discussion Chapter Nederlandse samenvatting Dankwoord/acknowledgements 199

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10 Preface Neurodegenerative disorders, a collection of more than 100 different diseases, are pathologies of the central nervous system (CNS). They are in general defined as progressive dysfunctions of the CNS, often associated with an advanced age and can be sporadic as well as hereditary (Przedborski et al., 2003). Examples, and most known diseases, are multiple sclerosis (MS), Parkinson s disease (PD), Alzheimer s disease (AD), Huntington s disease (HD) and amyotrophic lateral sclerosis (ALS). The degeneration of neurons in the brain and spinal cord is considered the main consequence of these pathologies. While these neurons have been and are still studied intensively, the focus has included the role of the immune system in these pathologies. The immune system is not a separate organ to just protect us from infectious diseases or germs, it is a much more complex system very intertwined with all the processes in our body. Therefore, a derailed immune system might lead to allergies and propagations of disorders, and in severe conditions to auto immune diseases. In this thesis, the role of the CNS resident immune cells and myeloid infiltrates from the periphery, originating in the bone marrow, are studied in the context of MS. 9

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