{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T20:55:55Z","timestamp":1758401755227,"version":"3.40.3"},"reference-count":38,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2012,8,28]],"date-time":"2012-08-28T00:00:00Z","timestamp":1346112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathology International"],"published-print":{"date-parts":[[2012,9]]},"abstract":"<jats:p>Rabies virus can cause fatal encephalomyelitis, but the involvement of extraneural organs has not been well characterized. In this study, we investigated the histopathological changes and the distribution of viral antigens in extraneural organs after pathogenic rabies virus infection in mouse and rat models. In histopathological examination, classical viral encephalitis and rabies\u2010specific Negri body were observed in the brain. In addition to the central nervous system (CNS), inflammatory responses were found in other organs, such as the heart, kidney, liver, and lung. Similarly, immunohistochemical staining and reverse transcription\u2010polymerase chain reaction revealed the presence of rabies virus in the CNS and extraneural tissues. Moreover, macrophages, especially in the lung and heart, were involved in the infection. Transcriptional analyses of the expression of inducible nitric oxide synthase (iNOS) demonstrated that rabies virus potentiated the gene expression of iNOS in the brain, lung, and heart. The immunoreactive iNOS\u2010positive macrophages were detected adjacent to the infection. These results suggest that macrophages are involved in the extraneural infection and the expression of iNOS in macrophages contributes to the formation of tissue inflammation. Our study indicates the involvement of extraneural organs following rabies virus infection, which may aggravate the progression of this deadly disease.<\/jats:p>","DOI":"10.1111\/j.1440-1827.2012.02846.x","type":"journal-article","created":{"date-parts":[[2012,8,28]],"date-time":"2012-08-28T09:31:40Z","timestamp":1346146300000},"page":"619-627","source":"Crossref","is-referenced-by-count":10,"title":["Involvement of extraneural tissues and upregulation of inducible nitric oxide synthase after experimental infection with rabies virus in BALB\/c mice and LEW\/SsN rats"],"prefix":"10.1111","volume":"62","author":[{"given":"Pi\u2010Hung","family":"Liao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yung\u2010Hsiang","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui\u2010Hua","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming\u2010Hseng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li\u2010Kuang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,8,28]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"1","article-title":"Consultation on rabies","volume":"931","author":"WHO Expert","year":"2005","journal-title":"World Health Organ Tech Rep Ser"},{"doi-asserted-by":"publisher","key":"e_1_2_6_3_2","DOI":"10.2217\/17460794.3.5.481"},{"doi-asserted-by":"publisher","key":"e_1_2_6_4_2","DOI":"10.1016\/j.ncl.2008.03.010"},{"key":"e_1_2_6_5_2","doi-asserted-by":"crossref","first-page":"128","DOI":"10.4103\/1117-1936.180501","article-title":"Rabies in apparently healthy dogs: Histological and immunohistochemical studies","volume":"13","author":"Ajayi BB","year":"2006","journal-title":"Niger Postgrad Med J"},{"doi-asserted-by":"publisher","key":"e_1_2_6_6_2","DOI":"10.1177\/030098589403100112"},{"key":"e_1_2_6_7_2","first-page":"877","article-title":"Detection of rabies virus in different tissues of experimentally infected mice at preclinical and postclinical stages of the disease","volume":"30","author":"Dutta MK","year":"1992","journal-title":"Indian J Exp Biol"},{"key":"e_1_2_6_8_2","doi-asserted-by":"crossref","first-page":"724","DOI":"10.2460\/ajvr.1984.45.04.724","article-title":"Peripheral distribution of virus in dogs inoculated with two strains of rabies virus","volume":"45","author":"Fekadu M","year":"1984","journal-title":"Am J Vet Res"},{"doi-asserted-by":"publisher","key":"e_1_2_6_9_2","DOI":"10.1007\/s00705-005-0785-0"},{"key":"e_1_2_6_10_2","first-page":"945","article-title":"Extraneural organ involvement in human rabies","volume":"79","author":"Jackson AC","year":"1999","journal-title":"Lab Invest"},{"doi-asserted-by":"publisher","key":"e_1_2_6_11_2","DOI":"10.1046\/j.1440-1789.2000.00332.x"},{"doi-asserted-by":"publisher","key":"e_1_2_6_12_2","DOI":"10.1080\/00313020802320689"},{"doi-asserted-by":"publisher","key":"e_1_2_6_13_2","DOI":"10.1016\/S1607-551X(09)70227-X"},{"doi-asserted-by":"publisher","key":"e_1_2_6_14_2","DOI":"10.1111\/j.1708-8305.2006.00095.x"},{"doi-asserted-by":"publisher","key":"e_1_2_6_15_2","DOI":"10.1001\/archneur.62.6.873"},{"doi-asserted-by":"publisher","key":"e_1_2_6_16_2","DOI":"10.1002\/lt.20580"},{"doi-asserted-by":"publisher","key":"e_1_2_6_17_2","DOI":"10.1111\/j.1399-3046.2005.00481.x"},{"doi-asserted-by":"publisher","key":"e_1_2_6_18_2","DOI":"10.1371\/journal.ppat.1000485"},{"doi-asserted-by":"publisher","key":"e_1_2_6_19_2","DOI":"10.1016\/S0022-1759(99)00223-9"},{"doi-asserted-by":"publisher","key":"e_1_2_6_20_2","DOI":"10.1177\/39.6.1709656"},{"key":"e_1_2_6_21_2","first-page":"339","article-title":"Rabies encephalomyelitis with myocarditis and pancreatitis. 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