Journal Article FZJ-2020-00857

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Crosstalk between stressed brain cells: direct and indirect effects of ischemia and aglycemia on microglia

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2020
BioMed Central London

Journal of neuroinflammation 17(1), 33 () [10.1186/s12974-020-1697-8]

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Abstract: BackgroundIn 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.MethodsWe 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.”ResultsOGD 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.ConclusionsData 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.

Classification:

Contributing Institute(s):
  1. Kognitive Neurowissenschaften (INM-3)
Research Program(s):
  1. 572 - (Dys-)function and Plasticity (POF3-572) (POF3-572)

Appears in the scientific report 2020
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Medline ; Creative Commons Attribution CC BY 4.0 ; DOAJ ; OpenAccess ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection
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Dokumenttypen > Aufsätze > Zeitschriftenaufsätze
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Open Access

 Datensatz erzeugt am 2020-02-04, letzte Änderung am 2021-01-30


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