{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T10:52:19Z","timestamp":1777632739011,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.pntd.0012188","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T00:00:00Z","timestamp":1717718400000}}],"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["MOST 104-2320-B-038-059"],"award-info":[{"award-number":["MOST 104-2320-B-038-059"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008398","name":"Villum Fonden","doi-asserted-by":"publisher","award":["Grant No. 9301"],"award-info":[{"award-number":["Grant No. 9301"]}],"id":[{"id":"10.13039\/100008398","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012331","name":"LEO Fondet","doi-asserted-by":"publisher","award":["LF-OC-20-000370"],"award-info":[{"award-number":["LF-OC-20-000370"]}],"id":[{"id":"10.13039\/501100012331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosntds.org"],"crossmark-restriction":false},"short-container-title":["PLoS Negl Trop Dis"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p><jats:italic>Angiostrongylus cantonensis<\/jats:italic> is a parasite that mainly infects the heart and pulmonary arteries of rats and causes human eosinophilic meningitis or meningoencephalitis in certain geographical areas. Current diagnostic methods include detection of the parasite in cerebrospinal fluid (CSF) and eosinophilic immune examination after lumbar puncture, which may be risky and produce false-positive results. <jats:sup>18<\/jats:sup>F- Fluorodeoxyglucose (FDG), a Positron emission tomography (PET) tracer, has been used to assess different pathological or inflammatory changes in the brains of patients. In this study, we hypothesized that <jats:italic>A<\/jats:italic>. <jats:italic>cantonensis<\/jats:italic> infection-induced inflammatory and immunomodulatory factors of eosinophils result in localized pathological changes in the brains of non-permissive hosts, which could be analyzed using <jats:italic>in vivo<\/jats:italic> <jats:sup>18<\/jats:sup>F-FDG PET imaging.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methodology\/Findings<\/jats:title>\n<jats:p>Non-permissive host ICR mice and permissive host SD rats were infected with <jats:italic>A<\/jats:italic>. <jats:italic>cantonensis<\/jats:italic>, and the effects of the resulting inflammation on <jats:sup>18<\/jats:sup>F-FDG uptake were characterized using PET imaging. We also quantitatively measured the distributed uptake values of different brain regions to build an evaluated imaging model of localized neuropathological damage caused by eosinophilic inflammation. Our results showed that the uptake of <jats:sup>18<\/jats:sup>F-FDG increased in the cerebellum, brainstem, and limbic system of mice at three weeks post-infection, whereas the uptake in the rat brain was not significant. Immunohistochemical staining and western blotting revealed that Iba-1, a microglia-specific marker, significantly increased in the hippocampus and its surrounding area in mice after three weeks of infection, and then became pronounced after four weeks of infection; while YM-1, an eosinophilic chemotactic factor, in the hippocampus and midbrain, increased significantly from two weeks post-infection, sharply escalated after three weeks of infection, and peaked after four weeks of infection. Cytometric bead array (CBA) analysis revealed that the expression of TNF in the serum of mice increased concomitantly with the prolongation of infection duration. Furthermore, IFN-\u03b3 and IL-4 in rat serum were significantly higher than in mouse serum at two weeks post-infection, indicating significantly different immune responses in the brains of rats and mice. We suggest that <jats:sup>18<\/jats:sup>F-FDG uptake in the host brain may be attributed to the accumulation of large numbers of immune cells, especially the metabolic burst of activated eosinophils, which are attracted to and induced by activated microglia in the brain.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>An <jats:italic>in vivo<\/jats:italic> <jats:sup>18<\/jats:sup>F-FDG\/PET imaging model can be used to evaluate live neuroinflammatory pathological changes in the brains of <jats:italic>A<\/jats:italic>. <jats:italic>cantonensis<\/jats:italic>-infected mice and rats.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pntd.0012188","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T18:39:39Z","timestamp":1716921579000},"page":"e0012188","update-policy":"https:\/\/doi.org\/10.1371\/journal.pntd.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Inflammatory and immunopathological differences in brains of permissive and non-permissive hosts with Angiostrongylus cantonensis infection can be identified using 18F\/FDG\/PET-imaging"],"prefix":"10.1371","volume":"18","author":[{"given":"Kang-wei","family":"Chang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lian-Chen","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hung-Yang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzu-Yuan","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edwin En-Te","family":"Hwu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1172-2485","authenticated-orcid":true,"given":"Po-Ching","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"issue":"4","key":"pntd.0012188.ref001","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/s10096-011-1328-5","article-title":"Human Angiostrongylus cantonensis: an update","volume":"31","author":"QP Wang","year":"2012","journal-title":"Eur J Clin Microbiol Infect Dis"},{"issue":"8624","key":"pntd.0012188.ref002","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1016\/S0140-6736(88)90905-1","article-title":"Angiostrongylus cantonensis and eosinophilic meningitis","volume":"2","author":"JE Alicata","year":"1988","journal-title":"Lancet"},{"issue":"10","key":"pntd.0012188.ref003","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/S1473-3099(08)70229-9","article-title":"Human angiostrongyliasis.","volume":"8","author":"QP Wang","year":"2008","journal-title":"Lancet Infect Dis"},{"issue":"6 Suppl 2","key":"pntd.0012188.ref004","first-page":"23","article-title":"The apple snail Pomacea canaliculata, a novel vector of the rat lungworm, Angiostrongylus cantonensis: its introduction, spread, and control in China.","volume":"72","author":"TB Yang","year":"2013","journal-title":"Hawaii J Med Public Health"},{"issue":"2","key":"pntd.0012188.ref005","first-page":"248","article-title":"Studies on growth and distribution of Angiostrongylus cantonensis larvae in Ampullarium canaliculatus","volume":"18","author":"D Chao","year":"1987","journal-title":"Southeast Asian J Trop Med Public Health"},{"issue":"5","key":"pntd.0012188.ref006","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.kjms.2010.12.013","article-title":"Eosinophilic meningitis risk associated with raw Ampullarium canaliculatus snails consumption.","volume":"27","author":"JJ Wang","year":"2011","journal-title":"Kaohsiung J Med Sci"},{"issue":"1","key":"pntd.0012188.ref007","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/0020-7519(75)90091-0","article-title":"Comparative studies on the life history of Angiostrongylus mackerrasae Bhaibulaya, 1968 and Angiostrongylus cantonensis (Chen, 1935).","volume":"5","author":"M. 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