Universität zu Köln

Ladwig, Anne, Walter, Helene Luise, Hucklenbroich, Joerg, Willuweit, Antje, Langen, Karl-Josef ORCID: 0000-0003-1101-5075, Fink, Gereon Rudolph, Rueger, Maria Adele and Schroeter, Michael (2017). Osteopontin Augments M2 Microglia Response and Separates M1-and M2-Polarized Microglial Activation in Permanent Focal Cerebral Ischemia. Mediat. Inflamm., 2017. LONDON: HINDAWI LTD. ISSN 1466-1861

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Abstract

Background. Focal cerebral ischemia induces distinct neuroinflammatory processes. We recently reported the extracellular phosphor-glyco-protein osteopontin (OPN) to directly affect primary microglia in vitro, promoting survival while shifting their inflammatory profile towards a more neutral phenotype. We here assessed the effects of OPN on microglia after stroke in vivo, with focus on infarct demarcation. Methods. Animals underwent focal photothrombotic stroke and were injected intracerebroventricularly with 500 mu g OPN or vehicle. Immunohistochemistry assessed neuronal damage and infarct volume, neovascularisation, glial scar formation, microglial activation, and M1 and M2 polarisation. Results. After photothrombotic stroke, areas covered by M1 and M2 microglia substantially overlapped. OPN treatment reduced that overlap, with microglia appearing more spread out and additionally covering the infarct core. OPN additionally modulated the quantity of microglia subpopulations, reducing iNOS+ M1 cells while increasing M2 microglia, shifting the M1/ M2 balance towards an M2 phenotype. Moreover, OPN polarized astrocytes towards the infarct. Conclusion. Microglial activation and M1 and M2 polarization have distinct but overlapping spatial patterns in permanent focal ischemia. Data suggest that OPN is involved in separating M1 and M2 subpopulations, as well as in shifting microglia polarization towards the M2 phenotype modulating beneficially inflammatory responses after focal infarction.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ladwig, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Walter, Helene Luise UNSPECIFIED UNSPECIFIED UNSPECIFIED Hucklenbroich, Joerg UNSPECIFIED UNSPECIFIED UNSPECIFIED Willuweit, Antje UNSPECIFIED UNSPECIFIED UNSPECIFIED Langen, Karl-Josef UNSPECIFIED orcid.org/0000-0003-1101-5075 UNSPECIFIED Fink, Gereon Rudolph UNSPECIFIED UNSPECIFIED UNSPECIFIED Rueger, Maria Adele UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeter, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-245503
DOI:	10.1155/2017/7189421
Journal or Publication Title:	Mediat. Inflamm.
Volume:	2017
Date:	2017
Publisher:	HINDAWI LTD
Place of Publication:	LONDON
ISSN:	1466-1861
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ALTERNATIVE ACTIVATION; CYTOKINE EXPRESSION; MACROPHAGES; STROKE; MICROGLIA/MACROPHAGES; NEUROINFLAMMATION; NEUROPROTECTION; NEUROGENESIS; POLARIZATION; INFLAMMATION Multiple languages Cell Biology; Immunology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/24550