ArticlePLoS pathogens2014
PPARγ agonists improve survival and neurocognitive outcomes in experimental cerebral malaria and induce neuroprotective pathways in human malaria.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic review of the role of angiopoietin-1 and angiopoietin-2 in Plasmodium species infections: biomarkers or therapeutic targets?Malaria journal · 2016Pooled it
- Safety and tolerability of adjunctive rosiglitazone treatment for children with uncomplicated malaria.Malaria journal · 2017Trial
- Evaluation of clinically approved neuroprotective drugs as adjunct therapies in experimental cerebral malaria.Archives of microbiology · 2026Article
- Malaria: past, present, and future.Signal transduction and targeted therapy · 2025Review
- Nilotinib attenuates vascular pathology in experimental cerebral malaria.Blood advances · 2025Article
- New mechanisms and therapeutic approaches to regulate vascular permeability in systemic inflammation.Current opinion in hematology · 2025Review
- Exploring adjunctive therapies for cerebral malaria.Frontiers in cellular and infection microbiology · 2024Review
- Vascular endothelial growth factor A: friend or foe in the pathogenesis of HIV and SARS-CoV-2 infections?Frontiers in cellular and infection microbiology · 2024Review
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
- Peroxisome proliferator-activated receptor-γ doesn't modify altered electrophysiological properties of the CA1 pyramidal neurons in a rat model of hepatic cirrhosis.Metabolic brain disease · 2022Article
- Cerebral Malaria and Neuronal Implications of Plasmodium Falciparum Infection: From Mechanisms to Advanced Models.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- Review
- Cerebral malaria induced byFrontiers in cellular and infection microbiology · 2022Review
- Malaria Related Neurocognitive Deficits and Behavioral Alterations.Frontiers in cellular and infection microbiology · 2022Review
- Signaling pathways and intervention therapies in sepsis.Signal transduction and targeted therapy · 2021Review
- Infectious disease-associated encephalopathies.Critical care (London, England) · 2021Review
- Randomized, phase 1/2, double-blind pioglitazone repositioning trial combined with antifungals for the treatment of cryptococcal meningitis - PIO study.Contemporary clinical trials communications · 2021Article
- Systemic Response to Infection Induces Long-Term Cognitive Decline: Neuroinflammation and Oxidative Stress as Therapeutical Targets.Frontiers in neuroscience · 2021Review
- Dimethyl fumarate reduces TNF and Plasmodium falciparum induced brain endothelium activation in vitro.Malaria journal · 2020Article
- Fever in returning travellers and migrants: disease severity markers to improve triage and management.Journal of travel medicine · 2020Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Cerebral malaria (CM) is associated with a high mortality rate, and long-term neurocognitive impairment in approximately one third of survivors. Adjunctive therapies that modify the pathophysiological processes involved in CM may improve outcome over anti-malarial therapy alone. PPARγ agonists have been reported to have immunomodulatory effects in a variety of disease models. Here we report that adjunctive therapy with PPARγ agonists improved survival and long-term neurocognitive outcomes in the Plasmodium berghei ANKA experimental model of CM. Compared to anti-malarial therapy alone, PPARγ adjunctive therapy administered to mice at the onset of CM signs, was associated with reduced endothelial activation, and enhanced expression of the anti-oxidant enzymes SOD-1 and catalase and the neurotrophic factors brain derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the brains of infected mice. Two months following infection, mice that were treated with anti-malarials alone demonstrated cognitive dysfunction, while mice that received PPARγ adjunctive therapy were completely protected from neurocognitive impairment and from PbA-infection induced brain atrophy. In humans with P. falciparum malaria, PPARγ therapy was associated with reduced endothelial activation and with induction of neuroprotective pathways, such as BDNF. These findings provide insight into mechanisms conferring improved survival and preventing neurocognitive injury in CM, and support the evaluation of PPARγ agonists in human CM.
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