ArticleMolecular neurobiology2017
A Neuroprotective Effect of the Glutamate Receptor Antagonist MK801 on Long-Term Cognitive and Behavioral Outcomes Secondary to Experimental Cerebral Malaria.
Article in Molecular neurobiology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
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- Interaction between transient receptor potential vanilloid 4 and glutamate NMDA receptor subunit 1 mediates endoplasmic reticulum stress and neuroinflammation in postoperative delirium.Molecular biomedicine · 2026Article
- Antimalarial and neuroprotective effects of ethanolic extracts of the five-flower remedy in an experimental cerebral malaria model.PloS one · 2025Article
- Unveiling new perspectives about the onset of neurological and cognitive deficits in cerebral malaria: exploring cellular and neurochemical mechanisms.Frontiers in cellular and infection microbiology · 2025Review
- Non-cerebral malaria: does such a thing exist?Memorias do Instituto Oswaldo Cruz · 2025Review
- A suitable model to investigate acute neurological consequences of coronavirus infection.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- 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
- Pathogenesis of Cerebral Malaria: New Trends and Insights for Developing Adjunctive Therapies.Pathogens (Basel, Switzerland) · 2023Article
- Interplay Between the Immune and Nervous Cognitive Systems in Homeostasis and in Malaria.International journal of biological sciences · 2023Review
- Malaria Related Neurocognitive Deficits and Behavioral Alterations.Frontiers in cellular and infection microbiology · 2022Review
- Restoration of Sarco/Endoplasmic Reticulum CaFrontiers in pharmacology · 2022Article
- Neurotransmitters and molecular chaperones interactions in cerebral malaria: Is there a missing link?Frontiers in molecular biosciences · 2022Review
- The effects of thymoquinone on memory impairment and inflammation in rats with hepatic encephalopathy induced by thioacetamide.Metabolic brain disease · 2021Article
- Systemic Response to Infection Induces Long-Term Cognitive Decline: Neuroinflammation and Oxidative Stress as Therapeutical Targets.Frontiers in neuroscience · 2021Review
- Mesenchymal stromal cells protect against vascular damage and depression-like behavior in mice surviving cerebral malaria.Stem cell research & therapy · 2020Article
- Olfactory Training Prevents Olfactory Dysfunction Induced by Bulbar Excitotoxic Lesions: Role of Neurogenesis and Dopaminergic Interneurons.Molecular neurobiology · 2019Article
- N-Methyl-D-Aspartate Receptors Involvement in the Gentamicin-Induced Hearing Loss and Pathological Changes of Ribbon Synapse in the Mouse Cochlear Inner Hair Cells.Neural plasticity · 2018Article
- Homeostasis of the Intraparenchymal-Blood Glutamate Concentration Gradient: Maintenance, Imbalance, and Regulation.Frontiers in molecular neuroscience · 2017Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cerebral malaria (CM) is a life-threatening complication of Plasmodium falciparum infection, which can result in long-term cognitive and behavioral deficits despite successful anti-malarial therapy. Due to the substantial social and economic burden of CM, the development of adjuvant therapies is a scientific goal of highest priority. Apart from vascular and immune responses, changes in glutamate system have been reported in CM pathogenesis suggesting a potential therapeutic target. Based on that, we hypothesized that interventions in the glutamatergic system induced by blockage of N-methyl-D-aspartate (NMDA) receptors could attenuate experimental CM long-term cognitive and behavioral outcomes. Before the development of evident CM signs, susceptible mice infected with Plasmodium berghei ANKA (PbA) strain were initiated on treatment with dizocilpine maleate (MK801, 0.5 mg/kg), a noncompetitive NMDA receptor antagonist. On day 5 post-infection, mice were treated orally with a 10-day course chloroquine (CQ, 30 mg/kg). Control mice also received saline, CQ or MK801 + CQ therapy. After 10 days of cessation of CQ treatment, magnetic resonance images (MRI), behavioral and immunological assays were performed. Indeed, MK801 combined with CQ prevented long-term memory impairment and depressive-like behavior following successful PbA infection resolution. In addition, MK801 also modulated the immune system by promoting a balance of TH1/TH2 response and upregulating neurotrophic factors levels in the frontal cortex and hippocampus. Moreover, hippocampus abnormalities observed by MRI were partially prevented by MK801 treatment. Our results indicate that NMDA receptor antagonists can be neuroprotective in CM and could be a valuable adjuvant strategy for the management of the long-term impairment observed in CM.
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