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.
Neurol Neuroimmunol Neuroinflamm. 2022 Jun 8;9(4). doi: 10.1212/NXI.0000000000001168. Print 2022 Jul.
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.
Active MOG 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.
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.
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.
实验研究表明，脑缺氧缺血和自身免疫性神经炎症存在共同的分子发病机制。这导致了一些临床试验，旨在研究已被批准用于多发性硬化症的免疫调节疗法对中风炎症损伤的影响。到目前为止，自身免疫、中枢神经系统抗原特异性炎症反应和脑缺血之间的相互和联合作用尚未得到研究。
在雄性 C57Bl/6J 小鼠中诱导活跃的 MOGEAE。在 EAE 的不同阶段，诱导短暂性大脑中动脉闭塞（tMCAO，60 分钟）。分析脑梗死面积和免疫细胞浸润。对与神经炎症和缺氧缺血损伤相关的 186 个基因进行多重基因表达分析。
患有严重 EAE 疾病的小鼠在 tMCAO 后梗死面积明显减小。组织病理学分析显示，严重疾病急性 EAE 小鼠梗死核心中的 CD45 造血细胞浸润减少；这伴随着 Arg1 阳性/Iba1 阳性细胞的积累。基因表达分析表明，在急性 EAE 阶段暴露于 tMCAO 的严重疾病小鼠中，髓样细胞驱动的抗炎机制参与了缺血损伤的减轻。
中枢神经系统自身抗原特异性自身免疫对实验性中风后的原发性组织损伤具有保护作用，表明在急性 EAE 阶段，中枢神经系统抗原特异性、与髓样细胞相关的抗炎免疫机制很早就参与其中，减轻了缺血性损伤。
