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In demyelinated areas, many hypertrophic astrocytes are present in close contact with oligodendrocytes, which often show apoptotic features. In the outermost layer of preserved myelin, stress proteins involved in tissue preconditioning are abundant in oligodendrocytes. The peri-plaque perimeter is thus assumed resistant to subsequent attack, thereby leaving a layer of preserved myelin. In some cases, Bal\u00f3\u2019s concentric rings develop step by step in a centrifugal direction, whereas many other cases show simultaneous enhancement of multiple rings. Therefore tissue preconditioning and successive ring formation does not fully describe the mechanism of the disease. We recently reported that in four Filipino Bal\u00f3\u2019s patients, aquaporin-4 (AQP4) was extensively lost in glial fibrillary acidic protein-positive hypertrophic astrocytes, both in demyelinated and myelinated layers of all actively demyelinating lesions. None of six further patients with MRI-confirmed Bal\u00f3\u2019s disease were seropositive for anti-AQP4 antibody. I propose that AQP4 astrocytopathy, in the absence of anti-AQP4 antibody, is characteristic of Bal\u00f3\u2019s disease. This hypothesis should be tested in future experimental studies.<\/jats:p>","DOI":"10.1177\/1352458511400475","type":"journal-article","created":{"date-parts":[[2011,4,1]],"date-time":"2011-04-01T20:43:04Z","timestamp":1301690584000},"page":"771-779","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":39,"title":["Astrocytopathy in Bal\u00f3\u2019s disease"],"prefix":"10.1177","volume":"17","author":[{"given":"Jun-ichi","family":"Kira","sequence":"first","affiliation":[{"name":"Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2011,4]]},"reference":[{"key":"e_1_3_4_2_2","first-page":"213","article-title":"Die so-genannte \u2018akute multiple Sklerose\u2019 (Encephalomyelitis periaxialis scleroticans)","volume":"28","author":"Marburg O","year":"1906","unstructured":"Marburg O. 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