Cerebral Malaria Model Applying Human Brain Organoids

Author:

Silva-Pedrosa Rita123ORCID,Campos Jonas12ORCID,Fernandes Aline Marie12,Silva Miguel4ORCID,Calçada Carla12,Marote Ana12ORCID,Martinho Olga12ORCID,Veiga Maria Isabel12ORCID,Rodrigues Ligia R.35ORCID,Salgado António José12,Ferreira Pedro Eduardo12ORCID

Affiliation:

1. Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus Gualtar, 4710-057 Braga, Portugal

2. ICVS/3B’s-PT Government Associate Laboratory, 4710-057 Braga, Portugal

3. CEB—Centre of Biological Engineering, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal

4. Department of Experimental Biology, Section of Microbiology, Faculty of Science, Masaryk University, Kamenice 753/5, 62500 Brno, Czech Republic

5. LABBELS—Associate Laboratory, 4710-057 Braga, Portugal

Abstract

Neural injuries in cerebral malaria patients are a significant cause of morbidity and mortality. 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–brain 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.

Publisher

MDPI AG

Subject

General Medicine

Reference122 articles.

1. (2023, January 16). World Malaria Report 2022. Available online: https://www.who.int/publications/i/item/9789240064898.

2. Pathophysiology and neurologic sequelae of cerebral malaria;Schiess;Malar. J.,2020

3. Endothelial Cells;Sturtzel;Adv. Exp. Med. Biol.,2017

4. Expression and regulation of toll-like receptors in cerebral endothelial cells;Wilhelm;Neurochem. Int.,2010

5. Regulation of NOD-like receptors and inflammasome activation in cerebral endothelial cells;Fazakas;J. Neurochem.,2015

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