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Nevertheless, a comprehensive research approach to study this issue is lacking, so herein we propose an in vitro system to study human cerebral malaria using cellular approaches. Our first goal was to establish a cellular system to identify the molecular alterations in human brain vasculature cells that resemble the blood\u2013brain barrier (BBB) in cerebral malaria (CM). Through transcriptomic analysis, we characterized specific gene expression profiles in human brain microvascular endothelial cells (HBMEC) activated by the Plasmodium falciparum parasites. We also suggest potential new genes related to parasitic activation. Then, we studied its impact at brain level after Plasmodium falciparum endothelial activation to gain a deeper understanding of the physiological mechanisms underlying CM. For that, the impact of HBMEC-P. falciparum-activated secretomes was evaluated in human brain organoids. Our results support the reliability of in vitro cellular models developed to mimic CM in several aspects. These systems can be of extreme importance to investigate the factors (parasitological and host) influencing CM, contributing to a molecular understanding of pathogenesis, brain injury, and dysfunction.<\/jats:p>","DOI":"10.3390\/cells12070984","type":"journal-article","created":{"date-parts":[[2023,3,24]],"date-time":"2023-03-24T04:31:05Z","timestamp":1679632265000},"page":"984","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cerebral Malaria Model Applying Human Brain Organoids"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1840-4033","authenticated-orcid":false,"given":"Rita","family":"Silva-Pedrosa","sequence":"first","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"},{"name":"CEB\u2014Centre of Biological Engineering, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8487-6621","authenticated-orcid":false,"given":"Jonas","family":"Campos","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"given":"Aline Marie","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8271-9910","authenticated-orcid":false,"given":"Miguel","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Experimental Biology, Section of Microbiology, Faculty of Science, Masaryk University, Kamenice 753\/5, 62500 Brno, Czech Republic"}]},{"given":"Carla","family":"Cal\u00e7ada","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0090-9196","authenticated-orcid":false,"given":"Ana","family":"Marote","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3221-0403","authenticated-orcid":false,"given":"Olga","family":"Martinho","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2205-8102","authenticated-orcid":false,"given":"Maria Isabel","family":"Veiga","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9265-0630","authenticated-orcid":false,"given":"Ligia R.","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"CEB\u2014Centre of Biological Engineering, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"LABBELS\u2014Associate Laboratory, 4710-057 Braga, Portugal"}]},{"given":"Ant\u00f3nio Jos\u00e9","family":"Salgado","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2682-7722","authenticated-orcid":false,"given":"Pedro Eduardo","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s-PT Government Associate Laboratory, 4710-057 Braga, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"key":"ref_1","unstructured":"(2023, January 16). 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