Universität zu Köln

Vay, Sabine Ulrike, Flitsch, Lea Jessica, Rabenstein, Monika, Rogall, Rebecca, Blaschke, Stefan, Kleinhaus, Judith, Reinert, Noemie, Bach, Annika, Fink, Gereon Rudolf, Schroeter, Michael and Rueger, Maria Adele (2018). The plasticity of primary microglia and their multifaceted effects on endogenous neural stem cells in vitro and in vivo. J. Neuroinflamm., 15. LONDON: BMC. ISSN 1742-2094

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Abstract

Background: Microglia-the resident immune cells of the brain-are activated after brain lesions, e.g., cerebral ischemia, and polarize towards a classic M1 pro-inflammatory or an alternative M2 anti-inflammatory phenotype following characteristic temporo-spatial patterns, contributing either to secondary tissue damage or to regenerative responses. They closely interact with endogenous neural stem cells (NSCs) residing in distinct niches of the adult brain. The current study aimed at elucidating the dynamics of microglia polarization and their differential effects on NSC function. Results: Primary rat microglia in vitro were polarized towards a M1 phenotype by LPS, or to a M2 phenotype by IL4, while simultaneous exposure to LPS plus IL4 resulted in a hybrid phenotype expressing both M1- and M2-characteristic markers. M2 microglia migrated less but exhibit higher phagocytic activity than M1 microglia. Defined mediators switched microglia from one polarization state to the other, a process more effective when transforming M2 microglia towards M1 than vice versa. Polarized microglia had differential effects on the differentiation potential of NSCs in vitro and in vivo, with M1 microglia promoting astrocytogenesis, while M2 microglia supported neurogenesis. Regardless of their polarization, microglia inhibited NSC proliferation, increased NSC migration, and accelerated NSC differentiation. Conclusion: Overall, this study shed light on the complex conditions governing microglia polarization and the effects of differentially polarized microglia on critical functions of NSCs in vitro and in vivo. Refining the understanding of microglia activation and their modulatory effects on NSCs is likely to facilitate the development of innovative therapeutic concepts supporting the innate regenerative capacity of the brain.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Vay, Sabine Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Flitsch, Lea Jessica UNSPECIFIED UNSPECIFIED UNSPECIFIED Rabenstein, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Rogall, Rebecca UNSPECIFIED UNSPECIFIED UNSPECIFIED Blaschke, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Kleinhaus, Judith UNSPECIFIED UNSPECIFIED UNSPECIFIED Reinert, Noemie UNSPECIFIED UNSPECIFIED UNSPECIFIED Bach, Annika UNSPECIFIED UNSPECIFIED UNSPECIFIED Fink, Gereon Rudolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeter, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Rueger, Maria Adele UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-176523
DOI:	10.1186/s12974-018-1261-y
Journal or Publication Title:	J. Neuroinflamm.
Volume:	15
Date:	2018
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1742-2094
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TRAUMATIC BRAIN-INJURY; CENTRAL-NERVOUS-SYSTEM; SPINAL-CORD-INJURY; M2 MICROGLIA; NEURODEGENERATIVE DISEASES; MACROPHAGE ACTIVATION; STEM/PROGENITOR CELLS; REACTIVE ASTROCYTES; CHRONIC PHASE; WHITE-MATTER Multiple languages Immunology; Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17652