{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:58:40Z","timestamp":1776214720333,"version":"3.50.1"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,8,29]],"date-time":"2021-08-29T00:00:00Z","timestamp":1630195200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP17fm0208023"],"award-info":[{"award-number":["JP17fm0208023"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["17fm0208021"],"award-info":[{"award-number":["17fm0208021"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","award":["18071245"],"award-info":[{"award-number":["18071245"]}],"id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,10,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Cerebral malaria (CM) is a life-threatening complication of the malaria disease caused by Plasmodium falciparum infection and is responsible for the death of half a million people annually. The molecular pathogenesis underlying CM in humans is not completely understood, although sequestration of infected erythrocytes in cerebral microvessels is thought to play a major role. In contrast, experimental cerebral malaria (ECM) models in mice have been thought to be distinct from human CM, and are mainly caused by inflammatory mediators. Here, to understand the spatial distribution and the potential sequestration of parasites in the whole-brain microvessels during a mouse model of ECM, we utilized the new tissue-clearing method CUBIC (Clear, Unobstructed, Brain\/Body Imaging Cocktails and Computational analysis) with light-sheet fluorescent microscopy (LSFM), and reconstructed images in three dimensions (3D). We demonstrated significantly greater accumulation of Plasmodium berghei ANKA (PbANKA) parasites in the olfactory bulb (OB) of mice, compared with the other parts of the brain, including the cerebral cortex, cerebellum and brainstem. Furthermore, we show that PbANKA parasites preferentially accumulate in the brainstem when the OB is surgically removed. This study therefore not only highlights a successful application of CUBIC tissue-clearing technology to visualize the whole brain and its microvessels during ECM, but it also shows CUBIC\u2019s future potential for visualizing pathological events in the whole ECM brain at the cellular level, an achievement that would greatly advance our understanding of human cerebral malaria.<\/jats:p>","DOI":"10.1093\/intimm\/dxab060","type":"journal-article","created":{"date-parts":[[2021,8,29]],"date-time":"2021-08-29T12:11:26Z","timestamp":1630239086000},"page":"587-594","source":"Crossref","is-referenced-by-count":4,"title":["Using a new three-dimensional CUBIC tissue-clearing method to examine the brain during experimental cerebral malaria"],"prefix":"10.1093","volume":"33","author":[{"given":"Julia","family":"Matsuo-Dapaah","sequence":"first","affiliation":[{"name":"Division of Malaria Immunology, Department of Microbiology and Immunology, Institute of Medical Science (IMSUT), University of Tokyo , Tokyo ,","place":["Japan"]},{"name":"Graduate School of Medicine, University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle Sue Jann","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Malaria Immunology, Department of Microbiology and Immunology, Institute of Medical Science (IMSUT), University of Tokyo , Tokyo ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6728-3872","authenticated-orcid":false,"given":"Ken J","family":"Ishii","sequence":"additional","affiliation":[{"name":"Graduate School of Medicine, University of Tokyo , Tokyo ,","place":["Japan"]},{"name":"Division of Vaccine Science, Department of Microbiology and Immunology, Institute of Medical Science (IMSUT), University of Tokyo , Tokyo ,","place":["Japan"]},{"name":"International Vaccine Design Center, Institute of Medical Science (IMSUT), University of Tokyo , Tokyo ,","place":["Japan"]},{"name":"Immunology Frontier Research Center (IFReC), Osaka University , Osaka ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kazuki","family":"Tainaka","sequence":"additional","affiliation":[{"name":"Department of System Pathology for Neurological Disorders, Center for Bioresources, Brain Research Institute, Niigata University , Niigata ,","place":["Japan"]},{"name":"Laboratory for Synthetic Biology, RIKEN Center for Biosystems Dynamics Research , Osaka ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4467-7799","authenticated-orcid":false,"given":"Cevayir","family":"Coban","sequence":"additional","affiliation":[{"name":"Division of Malaria Immunology, Department of Microbiology and Immunology, Institute of Medical Science (IMSUT), University of Tokyo , Tokyo ,","place":["Japan"]},{"name":"Graduate School of Medicine, University of Tokyo , Tokyo ,","place":["Japan"]},{"name":"International Vaccine Design Center, Institute of Medical Science (IMSUT), University of Tokyo , Tokyo ,","place":["Japan"]},{"name":"Immunology Frontier Research Center (IFReC), Osaka University , Osaka ,","place":["Japan"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2021,8,29]]},"reference":[{"key":"2026041420062680300_CIT0001","doi-asserted-by":"crossref","DOI":"10.30875\/7e6f8c91-en","volume-title":"World Malaria Report 2019","author":"World Health Organization","year":"2019"},{"key":"2026041420062680300_CIT0002","doi-asserted-by":"crossref","first-page":"2016","DOI":"10.3389\/fimmu.2018.02016","article-title":"Cerebral malaria in mouse and man","volume":"9","author":"Ghazanfari","year":"2018","journal-title":"Front. 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Med. Chem. Lett."}],"container-title":["International Immunology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/intimm\/advance-article-pdf\/doi\/10.1093\/intimm\/dxab060\/40811788\/dxab060.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/intimm\/article-pdf\/33\/11\/587\/44558275\/dxab060.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/intimm\/article-pdf\/33\/11\/587\/44558275\/dxab060.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T00:12:00Z","timestamp":1776211920000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/intimm\/article\/33\/11\/587\/6359340"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,29]]},"references-count":37,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2021,8,29]]},"published-print":{"date-parts":[[2021,10,29]]}},"URL":"https:\/\/doi.org\/10.1093\/intimm\/dxab060","relation":{},"ISSN":["1460-2377"],"issn-type":[{"value":"1460-2377","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2021,11,1]]},"published":{"date-parts":[[2021,8,29]]}}}