CNS Antigen-Specific Neuroinflammation Attenuates Ischemic Stroke With Involvement of Polarized Myeloid Cells

Kirsten Guse; Nina Hagemann; Lisa Thiele; Jana Remlinger; Anke Salmen; Robert Hoepner; Irene Keller; Patricia Meyer; Denis Grandgirard; Stephen L Leib; Erik Vassella; Giuseppe Locatelli; Dirk M Hermann; Andrew Chan

doi:10.1212/NXI.0000000000001168

CNS Antigen-Specific Neuroinflammation Attenuates Ischemic Stroke With Involvement of Polarized Myeloid Cells

Neurol Neuroimmunol Neuroinflamm. 2022 Jun 8;9(4):e1168. doi: 10.1212/NXI.0000000000001168. Print 2022 Jul.

Affiliations

¹ From the Department of Neurology (K.G., L.T., J.R., A.S., R.H., A.C.), Inselspital, Bern University Hospital, Department for BioMedical Research (DBMR), University of Bern, Switzerland; Department of Neurology (K.G., L.T.), St. Josef-Hospital, Ruhr-University, Bochum, Germany; Department of Neurology (N.H., D.M.H.), Chair of Vascular Neurology, Dementia and Ageing Research, University of Duisburg-Essen, Germany; Interfaculty Bioinformatics Unit and Swiss Institute of Bioinformatics (I.K.), Department for BioMedical Research (DBMR), Neuroinfection Laboratory (P.M., D.G., S.L.L.), Institute for Infectious Diseases, Institute of Pathology (E.V.), and Theodor Kocher Institute (G.L.), University of Bern, Switzerland.
² From the Department of Neurology (K.G., L.T., J.R., A.S., R.H., A.C.), Inselspital, Bern University Hospital, Department for BioMedical Research (DBMR), University of Bern, Switzerland; Department of Neurology (K.G., L.T.), St. Josef-Hospital, Ruhr-University, Bochum, Germany; Department of Neurology (N.H., D.M.H.), Chair of Vascular Neurology, Dementia and Ageing Research, University of Duisburg-Essen, Germany; Interfaculty Bioinformatics Unit and Swiss Institute of Bioinformatics (I.K.), Department for BioMedical Research (DBMR), Neuroinfection Laboratory (P.M., D.G., S.L.L.), Institute for Infectious Diseases, Institute of Pathology (E.V.), and Theodor Kocher Institute (G.L.), University of Bern, Switzerland. andrew.chan@insel.ch.

Abstract

Background and objectives: Experimental studies indicate shared molecular pathomechanisms in cerebral hypoxia-ischemia and autoimmune neuroinflammation. This has led to clinical studies investigating the effects of immunomodulatory therapies approved in multiple sclerosis on inflammatory damage in stroke. So far, mutual and combined interactions of autoimmune, CNS antigen-specific inflammatory reactions and cerebral ischemia have not been investigated so far.

Methods: Active MOG_35-55 experimental autoimmune encephalomyelitis (EAE) was induced in male C57Bl/6J mice. During different phases of EAE, transient middle cerebral artery occlusion (tMCAO, 60 minutes) was induced. Brain tissue was analyzed for infarct size and immune cell infiltration. Multiplex gene expression analysis was performed for 186 genes associated with neuroinflammation and hypoxic-ischemic damage.

Results: Mice with severe EAE disease showed a substantial reduction in infarct size after tMCAO. Histopathologic analysis showed less infiltration of CD45⁺ hematopoietic cells in the infarct core of severely diseased acute EAE mice; this was accompanied by an accumulation of Arginase1-positive/Iba1-positive cells. Gene expression analysis indicated an involvement of myeloid cell-driven anti-inflammatory mechanisms in the attenuation of ischemic injury in severely diseased mice exposed to tMCAO in the acute EAE phase.

Discussion: CNS autoantigen-specific autoimmunity has a protective influence on primary tissue damage after experimental stroke, indicating a very early involvement of CNS antigen-specific, myeloid cell-associated anti-inflammatory immune mechanisms that mitigate ischemic injury in the acute EAE phase.

MeSH terms

Animals
Encephalomyelitis, Autoimmune, Experimental*
Infarction
Ischemic Stroke*
Male
Mice
Mice, Inbred C57BL
Myeloid Cells / metabolism
Myeloid Cells / pathology
Neuroinflammatory Diseases
Stroke*