Osteopontin Augments M2 Microglia Response and Separates M1- and M2-Polarized Microglial Activation in Permanent Focal Cerebral Ischemia
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 phenoty...
Saved in:
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2017-01-01
|
| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2017/7189421 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850169882787708928 |
|---|---|
| author | Anne Ladwig Helene Luise Walter Jörg Hucklenbroich Antje Willuweit Karl-Josef Langen Gereon Rudolph Fink Maria Adele Rueger Michael Schroeter |
| author_facet | Anne Ladwig Helene Luise Walter Jörg Hucklenbroich Antje Willuweit Karl-Josef Langen Gereon Rudolph Fink Maria Adele Rueger Michael Schroeter |
| author_sort | Anne Ladwig |
| collection | DOAJ |
| description | 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 μg 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. |
| format | Article |
| id | doaj-art-a2ad0576039a486da11993d4ced49b45 |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-a2ad0576039a486da11993d4ced49b452025-08-20T02:20:37ZengWileyMediators of Inflammation0962-93511466-18612017-01-01201710.1155/2017/71894217189421Osteopontin Augments M2 Microglia Response and Separates M1- and M2-Polarized Microglial Activation in Permanent Focal Cerebral IschemiaAnne Ladwig0Helene Luise Walter1Jörg Hucklenbroich2Antje Willuweit3Karl-Josef Langen4Gereon Rudolph Fink5Maria Adele Rueger6Michael Schroeter7Department of Neurology, University Hospital of Cologne, Cologne, GermanyDepartment of Neurology, University Hospital of Cologne, Cologne, GermanyDepartment of Neurology, University Hospital of Cologne, Cologne, GermanyMedical Imaging Physics, Institute of Neuroscience and Medicine (INM-4), Research Centre Juelich, Juelich, GermanyMedical Imaging Physics, Institute of Neuroscience and Medicine (INM-4), Research Centre Juelich, Juelich, GermanyDepartment of Neurology, University Hospital of Cologne, Cologne, GermanyDepartment of Neurology, University Hospital of Cologne, Cologne, GermanyDepartment of Neurology, University Hospital of Cologne, Cologne, GermanyBackground. 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 μg 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.http://dx.doi.org/10.1155/2017/7189421 |
| spellingShingle | Anne Ladwig Helene Luise Walter Jörg Hucklenbroich Antje Willuweit Karl-Josef Langen Gereon Rudolph Fink Maria Adele Rueger Michael Schroeter Osteopontin Augments M2 Microglia Response and Separates M1- and M2-Polarized Microglial Activation in Permanent Focal Cerebral Ischemia Mediators of Inflammation |
| title | Osteopontin Augments M2 Microglia Response and Separates M1- and M2-Polarized Microglial Activation in Permanent Focal Cerebral Ischemia |
| title_full | Osteopontin Augments M2 Microglia Response and Separates M1- and M2-Polarized Microglial Activation in Permanent Focal Cerebral Ischemia |
| title_fullStr | Osteopontin Augments M2 Microglia Response and Separates M1- and M2-Polarized Microglial Activation in Permanent Focal Cerebral Ischemia |
| title_full_unstemmed | Osteopontin Augments M2 Microglia Response and Separates M1- and M2-Polarized Microglial Activation in Permanent Focal Cerebral Ischemia |
| title_short | Osteopontin Augments M2 Microglia Response and Separates M1- and M2-Polarized Microglial Activation in Permanent Focal Cerebral Ischemia |
| title_sort | osteopontin augments m2 microglia response and separates m1 and m2 polarized microglial activation in permanent focal cerebral ischemia |
| url | http://dx.doi.org/10.1155/2017/7189421 |
| work_keys_str_mv | AT anneladwig osteopontinaugmentsm2microgliaresponseandseparatesm1andm2polarizedmicroglialactivationinpermanentfocalcerebralischemia AT heleneluisewalter osteopontinaugmentsm2microgliaresponseandseparatesm1andm2polarizedmicroglialactivationinpermanentfocalcerebralischemia AT jorghucklenbroich osteopontinaugmentsm2microgliaresponseandseparatesm1andm2polarizedmicroglialactivationinpermanentfocalcerebralischemia AT antjewilluweit osteopontinaugmentsm2microgliaresponseandseparatesm1andm2polarizedmicroglialactivationinpermanentfocalcerebralischemia AT karljoseflangen osteopontinaugmentsm2microgliaresponseandseparatesm1andm2polarizedmicroglialactivationinpermanentfocalcerebralischemia AT gereonrudolphfink osteopontinaugmentsm2microgliaresponseandseparatesm1andm2polarizedmicroglialactivationinpermanentfocalcerebralischemia AT mariaadelerueger osteopontinaugmentsm2microgliaresponseandseparatesm1andm2polarizedmicroglialactivationinpermanentfocalcerebralischemia AT michaelschroeter osteopontinaugmentsm2microgliaresponseandseparatesm1andm2polarizedmicroglialactivationinpermanentfocalcerebralischemia |