Abstract
Targeting the immune system and thereby modulating the inflammatory response in ischemic stroke has shown promising therapeutic potential in various preclinical trials. Among those, intravenous immunoglobulins (IVIg) have moved into the focus of attention. In a murine model of experimental stroke, we explored the therapeutic potential of IVIg on the neurological outcome and the inflammatory response. Further, we used an in vitro system to assess effects of IVIg-stimulated microglia on neuronal survival. Treatment with IVIg resulted in decreased lesion sizes, without significant effects on the infiltration and activation pattern of peripheral immune cells. However, in microglia IVIg induced a switch towards an upregulation of protective polarization markers, and the ablation of microglia led to the loss of neuroprotective IVIg effects. Functionally, IVIg stimulated microglia ameliorated neuronal cell death elicited by oxygen and glucose deprivation in vitro. Notably, application of IVIg in vivo led to a comparable decrease of apoptotic neurons in the penumbra area. Although neuroprotective effects of IVIg in vivo and in vitro have been established in previous studies, we were able to show for the first time, that IVIg modulates the polarization of microglia during the pathogenesis of stroke.
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Acknowledgements
The authors thank Annika Ruhl, Oliver Schnapauff, and Ellen Orthey for excellent technical support. We also thank the FACS Core Facility of the UKE as well as Berta Puig-Martell for assistance with the imaging.
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This work was supported by Grants from the European Research Area Network/nEUROSurv (Dr. Magnus) and the Hermann und Lilly Schilling-Foundation for medical research (Dr. Magnus).
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BR: experimental design, critical revision of the article, CG: critical revision of the article, MG: experimental design, data generation and interpretation, drafting the article, TD: data generation and interpretation, TM: critical revision of the article, TVA: critical revision of the article, VH: Experimental design, data generation and interpretation, drafting the article, VR: Experimental design, data generation.
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Häußler, V., Daehn, T., Rissiek, B. et al. Intravenous Immunoglobulin (IVIg) Induce a Protective Phenotype in Microglia Preventing Neuronal Cell Death in Ischaemic Stroke. Neuromol Med 22, 121–132 (2020). https://doi.org/10.1007/s12017-019-08571-5
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DOI: https://doi.org/10.1007/s12017-019-08571-5