Lactate transport and receptor actions in cerebral malaria

Mariga, Shelton T.; Kolko, Miriam; Gjedde, Albert; Bergersen, Linda Hildegard

doi:10.3389/fnins.2014.00125

Cited by 15 publications

(13 citation statements)

References 64 publications

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“…Inflammation in bacterial meningitis is accompanied by a prominent increase of lactate concentrations in cerebrospinal fluid (CSF) and can be used as a reliable criterion for differential diagnosis of bacterial and aseptic meningitis [ 24 ], and/or viral meningitis [ 25 ]. Local production and transport of lactate within the NVU supports integration and normal functions of BBB [ 12 ] whereas elevated concentrations of lactate might be associated with neuroinflammation and BBB impairment [ 26 ]. Within the neurovascular unit, lactate is produced by neurons, perivascular astroglial cells, or BMECs.…”

Section: Introductionmentioning

confidence: 99%

The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood-brain barrier model in vitro

Boitsova

Моргун

Осипова

et al. 2018

J Neuroinflammation

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BackgroundLipopolysaccharide (LPS) is one of the main constituents of the cell wall of gram-negative bacteria. As an endotoxin, LPS induces neuroinflammation, which is associated with the blood-brain barrier impairment. Lactate is a metabolite with some significant physiological functions within the neurovascular unit/blood-brain barrier (BBB). Accumulation of extracellular and cerebrospinal fluid lactate is a specific feature of bacterial meningitis. However, the role of lactate production, transport, and sensing by lactate receptors GPR81 in the pathogenesis of bacterial neuroinflammation is still unknown.MethodsIn this study, we analyzed effects of LPS on the expression of GPR81 and MCT-1 and proliferation of cerebral endothelial cells in the BBB model in vitro. We used molecular profiling methods to measure the expression of GPR81, MCT-1, IL-1β, and Ki67 in the cerebral endothelium after treatment with different concentrations of LPS followed by measuring the level of extracellular lactate, transendothelial electric resistance, and permeability of the endothelial cell layer.ResultsOur findings showed that exposure to LPS results in neuroinflammatory changes associated with decreased expression of GPR81 and MCT-1 in endothelial cells, as well as overproduction of IL-1β and elevation of lactate concentrations in the extracellular space in a dose-dependent manner. LPS treatment reduced JAM tight junction protein expression in cerebral endothelial cells and altered BBB structural integrity in vitro.ConclusionThe impairment of lactate reception and transport might contribute to the alterations of BBB structural and functional integrity caused by LPS-mediated neuroinflammation.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1233-2) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood-brain barrier model in vitro

Boitsova

Моргун

Осипова

et al. 2018

J Neuroinflammation

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“…Transient and persistent neurocognitive impairments are also common among cerebral malaria survivors, mostly children (van der Wal et al, 2005 ; Idro et al, 2010 ). Several mechanisms have been hypothesized to play a role in the pathogenesis of CM including; mechanical obstruction of brain microvasculature by sequestered parasitized red blood cells (PRBCs), inflammation, hemostatic dysfunction, excessive parasite-derived lactate, and oxidative stress (Berendt et al, 1994 ; Medana et al, 2001 ; van der Heyde et al, 2006 ; Mariga et al, 2014 ). However, the exact pathogenesis of CM remains poorly understood and the various clinicopahtological features of human CM cannot be fully explained by the existing hypotheses (van der Heyde et al, 2006 ).…”

Section: Introductionmentioning

confidence: 99%

Potential role of Plasmodium falciparum-derived ammonia in the pathogenesis of cerebral malaria

Kimoloi

Rashid

2015

Front. Neurosci.

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Cerebral malaria (CM) is the most severe complication associated with Plasmodium falciparum infection. The exact pathogenic mechanisms leading to the development of CM remains poorly understood while the mortality rates remain high. Several potential mechanisms including mechanical obstruction of brain microvasculature, inflammation, oxidative stress, cerebral energy defects, and hemostatic dysfunction have been suggested to play a role in CM pathogenesis. However, these proposed mechanisms, even when considered together, do not fully explain the pathogenesis and clinicopathological features of human CM. This necessitates consideration of alternative pathogenic mechanisms. P. falciparum generates substantial amounts of ammonia as a catabolic by-product, but lacks detoxification mechanisms. Whether this parasite-derived ammonia plays a pathogenic role in CM is presently unknown, despite its potential to cause localized brain ammonia elevation and subsequent neurotoxic effects. This article therefore, explores and proposes a potential role of parasite-derived ammonia in the pathogenesis and neuropathology of CM. A consideration of parasite-derived ammonia as a factor in CM pathogenesis provides plausible explanations of the various features observed in CM patients including how a largely intravascular parasite can cause neuronal dysfunction. It also provides a framework for rational development and testing of novel drugs targeting the parasite's ammonia handling.

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“…increasing oxygen supply) decreased blood lactate levels and improved respiratory abnormalities . Lactate could possibly also have a damaging effect on brain endothelium during CM (Mariga et al 2014). Hyperlactatemia may have different origins, including production by the parasite itself and by uncontrolled muscle contraction during seizures (Orringer et al 1977;Krishna et al 1994).…”

Section: Metabolic Changesmentioning

confidence: 99%

The immunological balance between host and parasite in malaria

Deroost

Pham

Opdenakker

et al. 2015

FEMS Microbiology Reviews

116

143

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One sentence summary: The intricate balance between anti-malarial immunity and parasite virulence factors including immune evasion mechanisms determine the outcome of malaria infections, as imbalances resulting in exaggerated parasite growth, excessive inflammation or the combination of both result in severe pathology. Editor: Christian van Ooij ABSTRACTCoevolution of humans and malaria parasites has generated an intricate balance between the immune system of the host and virulence factors of the parasite, equilibrating maximal parasite transmission with limited host damage. Focusing on the blood stage of the disease, we discuss how the balance between anti-parasite immunity versus immunomodulatory and evasion mechanisms of the parasite may result in parasite clearance or chronic infection without major symptoms, whereas imbalances characterized by excessive parasite growth, exaggerated immune reactions or a combination of both cause severe pathology and death, which is detrimental for both parasite and host. A thorough understanding of the immunological balance of malaria and its relation to other physiological balances in the body is of crucial importance for developing effective interventions to reduce malaria-related morbidity and to diminish fatal outcomes due to severe complications. Therefore, we discuss in this review the detailed mechanisms of anti-malarial immunity, parasite virulence factors including immune evasion mechanisms and pathogenesis. Furthermore, we propose a comprehensive classification of malaria complications according to the different types of imbalances.

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Lactate transport and receptor actions in cerebral malaria

Cited by 15 publications

References 64 publications

The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood-brain barrier model in vitro

The inhibitory effect of LPS on the expression of GPR81 lactate receptor in blood-brain barrier model in vitro

Potential role of Plasmodium falciparum-derived ammonia in the pathogenesis of cerebral malaria

The immunological balance between host and parasite in malaria

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