ArticleScientific reports2019
Modelling heme-mediated brain injury associated with cerebral malaria in human brain cortical organoids.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers, 1 of them a synthesis that pooled it.
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Who cites it
33 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Mapping the Cerebral Organoid Landscape: A Systematic Review of Preclinical 3D Models in Neuroscience.Advanced healthcare materials · 2026Pooled it
- Beyond the mouse: organoids, spheroids, and organs-on-chips as the (inevitable) future of malaria research?Malaria journal · 2026Review
- Lessons on multicellular two- (2D) and three-dimensional (3D) culture in parasitology: Insights, challenges and future directions.International journal for parasitology · 2026Review
- Erythropoietin in tissue engineering and beyond: a multifunctional macromolecule with emerging roles in organoids, immune modulation, and cancer research.Frontiers in bioengineering and biotechnology · 2026Review
- Plasmodium falciparum egress disrupts endothelial junctions and activates JAK-STAT signaling in a microvascular 3D blood-brain barrier model.Nature communications · 2025Article
- Role of mast cell-derived exosomes in exacerbating neuronal injury of experimental cerebral malaria.Parasites & vectors · 2025Article
- Hemozoin induces malaria via activation of DNA damage, p38 MAPK and neurodegenerative pathways in a human iPSC-derived neuronal model of cerebral malaria.Scientific reports · 2024Article
- Article
- Human 3D brain organoids: steering the demolecularization of brain and neurological diseases.Cell death discovery · 2023Review
- Human brain microphysiological systems in the study of neuroinfectious disorders.Experimental neurology · 2023Review
- Human pluripotent stem cell (hPSC) and organoid models of autism: opportunities and limitations.Translational psychiatry · 2023Review
- Neural cortical organoids from self-assembling human iPSC as a model to investigate neurotoxicity in brain ischemia.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2023Article
- Article
- Review
- Neuregulin-1 attenuates hemolysis- and ischemia induced-cerebrovascular inflammation associated with sickle cell disease.Journal of stroke and cerebrovascular diseases : the official journal of National Stroke Association · 2023Article
- Modelling host-F1000Research · 2023Article
- Cerebral Malaria and Neuronal Implications of Plasmodium Falciparum Infection: From Mechanisms to Advanced Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- Modeling infectious diseases of the central nervous system with human brain organoids.Translational research : the journal of laboratory and clinical medicine · 2022Review
- Hastening Progress inMicroorganisms · 2022Article
- Advances in construction and modeling of functional neural circuits in vitro.Neurochemical research · 2022Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Human cerebral malaria (HCM), a severe encephalopathy associated with Plasmodium falciparum infection, has a 20-30% mortality rate and predominantly affects African children. The mechanisms mediating HCM-associated brain injury are difficult to study in human subjects, highlighting the urgent need for non-invasive ex vivo human models. HCM elevates the systemic levels of free heme, which damages the blood-brain barrier and neurons in distinct regions of the brain. We determined the effects of heme on induced pluripotent stem cells (iPSCs) and a three-dimensional cortical organoid system and assessed apoptosis and differentiation. We evaluated biomarkers associated with heme-induced brain injury, including a pro-inflammatory chemokine, CXCL-10, and its receptor, CXCR3, brain-derived neurotrophic factor (BDNF) and a receptor tyrosine-protein kinase, ERBB4, in the organoids. We then tested the neuroprotective effect of neuregulin-1 (NRG-1) against heme treatment in organoids. Neural stem and mature cells differentially expressed CXCL-10, CXCR3, BDNF and ERBB4 in the developing organoids and in response to heme-induced neuronal injury. The organoids underwent apoptosis and structural changes that were attenuated by NRG-1. Thus, cortical organoids can be used to model heme-induced cortical brain injury associated with HCM pathogenesis as well as for testing agents that reduce brain injury and neurological sequelae.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.