Universität zu Köln

Rabenstein, Monika, Vay, Sabine Ulrike, Blaschke, Stefan, Walter, Helene Luise, Ladwig, Anne, Fink, Gereon Rudolf, Rueger, Maria Adele and Schroeter, Michael (2020). Crosstalk between stressed brain cells: direct and indirect effects of ischemia and aglycemia on microglia. J. Neuroinflamm., 17 (1). LONDON: BMC. ISSN 1742-2094

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Abstract

Background In cerebral ischemia, microglia have a dichotomous role in keeping the balance between pro- and anti-inflammatory mediators to avoid deleterious chronic inflammation and to leverage repair processes. Methods We examined functional and inflammatory markers in primary rat microglia in vitro after oxygen-glucose deprivation (OGD) or glucose deprivation (aglycemia). We then investigated the preconditioning effect of OGD or aglycemia upon a subsequent strong inflammatory stimulus, here lipopolysaccharides (LPS). Moreover, an in vitro brain model of neurons and glia, differentiated from primary rat neural stem cells, was exposed to OGD or aglycemia. Conditioned medium (CM) of this neuronal/glial co-culture was then used to condition microglia, followed by LPS as a second hit. Results OGD or aglycemia at sublethal doses did not significantly affect microglia function, including the expression of inflammatory markers. However, preconditioning with either OGD or aglycemia led to a decreased pro-inflammatory response to a subsequent stimulus with LPS. Interestingly, the anti-inflammatory markers IGF-1 and IL-10 were additionally reduced after such preconditioning, while expression of CD206 remained unaffected. Treatment with CM from the neuronal/glial co-culture alone did not affect the expression of inflammatory markers in microglia. In contrast, treatment with CM increased the expression of both pro- and anti-inflammatory markers in microglia upon a second hit with LPS. Interestingly, this effect could be attenuated in microglia treated with CM from neuronal/glia co-cultures preconditioned with OGD or aglycemia. Conclusions Data suggest specific and distinct microglia signatures in response to metabolic stress. While metabolic stress directly and indirectly applied to microglia did not mitigate their subsequent response to inflammation, preconditioning with metabolic stress factors such as OGD and aglycemia elicited a decreased inflammatory response to a subsequent inflammation stimulus.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rabenstein, Monika UNSPECIFIED UNSPECIFIED UNSPECIFIED Vay, Sabine Ulrike UNSPECIFIED UNSPECIFIED UNSPECIFIED Blaschke, Stefan UNSPECIFIED UNSPECIFIED UNSPECIFIED Walter, Helene Luise UNSPECIFIED UNSPECIFIED UNSPECIFIED Ladwig, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Fink, Gereon Rudolf UNSPECIFIED UNSPECIFIED UNSPECIFIED Rueger, Maria Adele UNSPECIFIED UNSPECIFIED UNSPECIFIED Schroeter, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-348303
DOI:	10.1186/s12974-020-1697-8
Journal or Publication Title:	J. Neuroinflamm.
Volume:	17
Number:	1
Date:	2020
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	1742-2094
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language INJURY; POLARIZATION; EXPRESSION; TOLERANCE Multiple languages Immunology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/34830