Guse, Kirsten; Hagemann, Nina; Thiele, Lisa; Remlinger, Jana; Salmen, Anke; Hoepner, Robert; Keller, Irene; Meyer, Patricia; Grandgirard, Denis; Leib, Stephen; Vassella, Erik; Locatelli, Giuseppe; Hermann, Dirk M; Chan, Andrew Hao-Kuang (2022). CNS Antigen-Specific Neuroinflammation Attenuates Ischemic Stroke With Involvement of Polarized Myeloid Cells. Neurology: neuroimmunology & neuroinflammation, 9(4) Wolters Kluwer Health 10.1212/NXI.0000000000001168
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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 MOG35-55 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.
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