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Therefore, we investigated the distribution patterns of microglia and macrophages in 10 concentric lesions from four autopsied Bal\u00f3's disease cases and one neuromyelitis optica spectrum disorder (NMOSD) case, using quantitative immunohistochemistry for the markers TMEM119, P2RY12, CD68, CD163 and GLUT5. Three cases with Bal\u00f3's disease had distal oligodendrogliopathy (DO) showing preferential loss of myelin\u2010associated glycoprotein and early active demyelination in the outermost demyelinating layer (termed DMY\u2010MO). In DMY\u2010MO with DO, TMEM119\u2010positive activated microglia expressing upregulated GLUT5 but markedly downregulated P2RY12 were significantly increased. These activated microglia expressed inducible nitric oxide synthase. Oligodendrocytes and their precursors showed apoptotic\u2010like nuclear condensation in DMY\u2010MO. TMEM119\u2010negative and CD68\/CD163\u2010positive macrophages were distributed throughout the lesion center of DMY\u2010MO with DO and these cells demonstrated foamy morphology only in the inner portion but not in the outer portion. In concentric demyelinating lesions from another Bal\u00f3's case and lamellar demyelinating lesions in an NMOSD case, which had late active demyelination without DO, the densities of TMEM119\u2010, GLUT5\u2010 and P2RY12\u2010positive microglia with ramified morphology were significantly increased in myelinated layers but not in demyelinating layers. In particular, in the NMOSD case, TMEM119\u2010positive microglia were confined to the outer portion of the myelinated layers. CD68\u2010positive macrophages with foamy morphology also expressing CD163 accumulated in myelinated as well as in demyelinated layers. These findings suggest that activated microglia expressing TMEM119 and GLUT5, but not P2RY12, are associated with apoptosis of oligodendrocytes in the leading edge of Bal\u00f3's concentric lesions with DO, whereas TMEM119\u2010, GLUT5\u2010 and P2RY12\u2010positive microglia with ramified morphology are associated with myelin preservation in concentric lesions without DO in Bal\u00f3's disease and NMOSD. These two types of microglia appear to play distinct roles in the formation of concentric lesions.<\/jats:p>","DOI":"10.1111\/bpa.12898","type":"journal-article","created":{"date-parts":[[2020,9,22]],"date-time":"2020-09-22T08:11:40Z","timestamp":1600762300000},"page":"1144-1157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Distinct microglial and macrophage distribution patterns in the concentric and lamellar lesions in Bal\u00f3's disease and neuromyelitis optica spectrum disorders"],"prefix":"10.1111","volume":"30","author":[{"given":"Shotaro","family":"Hayashida","sequence":"first","affiliation":[{"name":"Department of Neurology Neurological Institute Graduate School of Medical Sciences Kyushu University Fukuoka 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