{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T08:04:43Z","timestamp":1778313883813,"version":"3.51.4"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T00:00:00Z","timestamp":1585699200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["A085 in 2019"],"award-info":[{"award-number":["A085 in 2019"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K07095"],"award-info":[{"award-number":["17K07095"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K08760"],"award-info":[{"award-number":["17K08760"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Neuropathology"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:p>Excessive production of nitric oxide (NO) due to the overinduction of inducible nitric oxide synthase (iNOS) has a severe cytotoxic effect, which may relate to the pathogenesis of neurodegenerative disorders. In this study, we report the novel finding that iNOS is overinduced in a large number of bizarre astrocytes in the white matter of patients with panencephalopathic (PE)\u2010type Creutzfeldt\u2013Jakob disease (CJD). This study was carried out on brain tissue from seven patients with PE\u2010type CJD. As controls, 12 normal individuals and nine patients with cerebral infarction were examined. We identified a large number of bizarre astrocytes in the degenerative cerebral white matter in PE\u2010type CJD. Using immunohistochemistry, only bizarre astrocytes in PE\u2010type CJD showed strong immunoreactivity for both iNOS and superoxide dismutase 1 (SOD1). Ultrastructural examination demonstrated that these bizarre astrocytes contained many free polyribosome\u2010like granules. No significant iNOS immunoreactivity was observed in either the astrocytes of patients with cerebral infarcts or in the normal controls. This study suggests that the iNOS\u2010overexpressing astrocytes, especially iNOS\u2010overexpressing bizarre astrocytes, could play an important role in the development of white matter lesions in PE\u2010type CJD. Our data also suggest that the bizarre astrocytes could be protecting themselves from the cytotoxicity of NO by producing SOD1. These immunohistochemical findings are supported by the ultrastructural observation of numerous polyribosome granules restricted to the cytoplasm of these bizarre astrocytes.<\/jats:p>","DOI":"10.1111\/neup.12646","type":"journal-article","created":{"date-parts":[[2020,4,1]],"date-time":"2020-04-01T07:17:49Z","timestamp":1585725469000},"page":"319-327","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Immunohistochemical and ultrastructural evidence for the pathogenesis of white matter degeneration in patients with panencephalopathic\u2010type Creutzfeldt\u2013Jakob disease: Inducible nitric oxide synthase overexpression in bizarre astrocytes"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8432-3602","authenticated-orcid":false,"given":"Hiroshi","family":"Kohama","sequence":"first","affiliation":[{"name":"Division of Neuropathology, Faculty of Medicine Tottori University  Yonago Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahiro","family":"Kusunoki\u2010Ii","sequence":"additional","affiliation":[{"name":"Division of Neuropathology, Faculty of Medicine Tottori University  Yonago Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kiyota","family":"Kato","sequence":"additional","affiliation":[{"name":"School of Medicine Hiroshima University  Hiroshima Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masako","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Pathology, Faculty of Medicine Tottori University  Yonago Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shinsuke","family":"Kato","sequence":"additional","affiliation":[{"name":"Division of Neuropathology, Faculty of Medicine Tottori University  Yonago Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,4]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.6801762"},{"key":"e_1_2_7_3_1","first-page":"1285","article-title":"Abnormal isoform of prion proteins accumulates in the synaptic structures of the central nervous system in patients with Creutzfeldt\u2010Jakob disease","volume":"140","author":"Kitamoto T","year":"1992","journal-title":"Am J Pathol"},{"key":"e_1_2_7_4_1","first-page":"903","article-title":"Neuropathology of Creutzfeldt\u2010Jakob disease in Japan. With special reference to the panencephalopathic type","volume":"31","author":"Mizutani T","year":"1981","journal-title":"Acta Pathol Jpn"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp.44.2.103"},{"key":"e_1_2_7_6_1","first-page":"139","volume-title":"Neuropsychiatric Disorders in the Elderly","author":"Shiraki H","year":"1983"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470123119.ch8"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-120-3-199402010-00009"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pa.35.040195.001241"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.6.12.1381691"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.55.2.175"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.1995.6"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.182.4.941"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.14-09-05147.1994"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.64010085.x"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-002-0646-1"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(84)90226-4"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010050983"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010000226"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010000355"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-003-0791-1"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-005-1019-3"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005072-199655100-00009"},{"key":"e_1_2_7_24_1","first-page":"611","article-title":"Pathological characterization of astrocytic hyaline inclusions in familial amyotrophic lateral sclerosis","volume":"151","author":"Kato S","year":"1997","journal-title":"Am J Pathol"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010100409"},{"key":"e_1_2_7_26_1","first-page":"230","article-title":"Formic acid pretreatment enhances immunostaining of cerebral and systemic amyloids","volume":"57","author":"Kitamoto T","year":"1987","journal-title":"Lab Invest"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2990.1997.tb01182.x"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010050977"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1201\/b13319-17"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00227673"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.13.6.455"},{"key":"e_1_2_7_32_1","first-page":"452","article-title":"Two autopsy cases of Creutzfeldt\u2010Jakob disease","volume":"16","author":"Kinoshita J","year":"1972","journal-title":"Adv Neurol Sci (Japan)"},{"key":"e_1_2_7_33_1","first-page":"726","volume-title":"Handbook of Clinical Neurology","author":"Rossum VA","year":"1968"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.10.5795"},{"key":"e_1_2_7_35_1","first-page":"87","volume-title":"Normal, Reactive and Neoplastic","author":"Duffy PE","year":"1983"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-642-68970-3_9"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/9780470123041.ch2"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.23.1.75"},{"key":"e_1_2_7_39_1","first-page":"551","volume-title":"Molecular Biology of the Cell","author":"Walter P","year":"1994"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.28.16856"}],"container-title":["Neuropathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fneup.12646","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/neup.12646","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/neup.12646","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/am-pdf\/10.1111%2Fneup.12646","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/neup.12646","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T21:18:46Z","timestamp":1693948726000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/neup.12646"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,4]]},"references-count":39,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1111\/neup.12646"],"URL":"https:\/\/doi.org\/10.1111\/neup.12646","archive":["Portico"],"relation":{},"ISSN":["0919-6544","1440-1789"],"issn-type":[{"value":"0919-6544","type":"print"},{"value":"1440-1789","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,4]]},"assertion":[{"value":"2019-08-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-01-07","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}