ArticlePLoS pathogens2012
Statins decrease neuroinflammation and prevent cognitive impairment after cerebral malaria.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02225834 (Effects of Early Atorvastatin Treatment During the Acute Phase of Stroke on Immunoinflammatory Markers and Outcome in Patients With Acute Ischemic Stroke Classified as LAAS According TOAST Classification), which is not on this map. Cited by 65 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effects of Early Atorvastatin Treatment During the Acute Phase of Stroke on Immunoinflammatory Markers and Outcome in Patients With Acute Ischemic Stroke Classified as LAAS According TOAST Classification
Who cites it
65 citing papers in PubMed, 104 citations in OpenAlex.
- Trial
- Lovastatin Potentiates the Function of α7-Nicotinic Acetylcholine Receptors.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Influence of blood-brain barrier and intestinal barrier on microglial phenotypes: a perspective of clinical and prognostic implications.Frontiers in immunology · 2026Article
- Potential Role of Red Yeast Rice in the Prevention and Treatment of Alzheimer's Disease.International journal of medical sciences · 2026Review
- The therapeutic potential of atorvastatin in treatment ofFrontiers in veterinary science · 2026Article
- The canine blood-brain barrier in health and disease: focus on brain protection.The veterinary quarterly · 2025Review
- Daily high doses of atorvastatin alter neuronal morphology in a juvenile songbird model.PloS one · 2025Article
- Antimalarial and neuroprotective effects of ethanolic extracts of the five-flower remedy in an experimental cerebral malaria model.PloS one · 2025Article
- Article
- Exploring adjunctive therapies for cerebral malaria.Frontiers in cellular and infection microbiology · 2024Review
- Pathogenetic mechanisms and treatment targets in cerebral malaria.Nature reviews. Neurology · 2023Review
- Efficacy of artesunate combined with Atractylodes lancea or Prabchompoothaweep remedy extracts as adjunctive therapy for the treatment of cerebral malaria.BMC complementary medicine and therapies · 2023Article
- Antiplasmodial, Trypanocidal, and GenotoxicityPharmaceuticals (Basel, Switzerland) · 2023Article
- Interplay Between the Immune and Nervous Cognitive Systems in Homeostasis and in Malaria.International journal of biological sciences · 2023Review
- Pre-treatment and continuous administration of simvastatin during sepsis improve metabolic parameters and prevent CNS injuries in survivor rats.Molecular and cellular biochemistry · 2022Article
- Treatment Reducing Endothelial Activation Protects against Experimental Cerebral Malaria.Pathogens (Basel, Switzerland) · 2022Article
- Pipecolic Acid, a Putative Mediator of the Encephalopathy of Cerebral Malaria and the Experimental Model of Cerebral Malaria.The Journal of infectious diseases · 2022Article
- Simvastatin Improves Microcirculatory Function in Nonalcoholic Fatty Liver Disease and Downregulates Oxidative and ALE-RAGE Stress.Nutrients · 2022Article
- NADPH Oxidase: a Possible Therapeutic Target for Cognitive Impairment in Experimental Cerebral Malaria.Molecular neurobiology · 2022Article
- Euterpe oleracea fruit (Açai)-enriched diet suppresses the development of experimental cerebral malaria induced by Plasmodium berghei (ANKA) infection.BMC complementary medicine and therapies · 2022Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Cerebral malaria (CM) is the most severe manifestation of Plasmodium falciparum infection in children and non-immune adults. Previous work has documented a persistent cognitive impairment in children who survive an episode of CM that is mimicked in animal models of the disease. Potential therapeutic interventions for this complication have not been investigated, and are urgently needed. HMG-CoA reductase inhibitors (statins) are widely prescribed for cardiovascular diseases. In addition to their effects on the inhibition of cholesterol synthesis, statins have pleiotropic immunomodulatory activities. Here we tested if statins would prevent cognitive impairment in a murine model of cerebral malaria. Six days after infection with Plasmodium berghei ANKA (PbA) mice displayed clear signs of CM and were treated with chloroquine, or chloroquine and lovastatin. Intravital examination of pial vessels of infected animals demonstrated a decrease in functional capillary density and an increase in rolling and adhesion of leukocytes to inflamed endothelium that were reversed by treatment with lovastatin. In addition, oedema, ICAM-1, and CD11b mRNA levels were reduced in lovastatin-treated PbA-infected mice brains. Moreover, HMOX-1 mRNA levels are enhanced in lovastatin-treated healthy and infected brains. Oxidative stress and key inflammatory chemokines and cytokines were reduced to non-infected control levels in animals treated with lovastatin. Fifteen days post-infection cognitive dysfunction was detected by a battery of cognition tests in animals rescued from CM by chloroquine treatment. In contrast, it was absent in animals treated with lovastatin and chloroquine. The outcome was similar in experimental bacterial sepsis, suggesting that statins have neuroprotective effects in severe infectious syndromes in addition to CM. Statin treatment prevents neuroinflammation and blood brain barrier dysfunction in experimental CM and related conditions that are associated with cognitive sequelae, and may be a valuable adjuvant therapeutic agent for prevention of cognitive impairment in patients surviving an episode of CM.
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