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cerebral malaria

Haplotype of RNASE 3 polymorphisms is associated with severe malaria in an Indian population

October 31, 2020 - 09:53 -- Open Access
Author(s): 
Mukhi B, Gupta H, Wassmer SC, Anvikar AR, Ghosh SK
Reference: 
Mol Biol Rep. 2020 Oct 28

Severe malaria (SM) caused by Plasmodium falciparum (Pf) infection has been associated with life-threatening anemia, metabolic acidosis, cerebral malaria and multiorgan dysfunction. It may lead to death if not treated promptly. RNASE 3 has been linked to Pf growth inhibition and its polymorphisms found associated with SM and cerebral malaria in African populations.

Dimethyl fumarate reduces TNF and Plasmodium falciparum induced brain endothelium activation in vitro

October 22, 2020 - 15:42 -- Open Access
Author(s): 
Neida K. Mita-Mendoza, Ariel Magallon-Tejada, Priyanka Parmar, Raquel Furtado, Margaret Aldrich, Alex Saidi, Terrie Taylor, Joe Smith, Karl Seydel and Johanna P. Daily
Reference: 
Malaria Journal 2020 19:376, 21 October 2020

Cerebral malaria (CM) is associated with morbidity and mortality despite the use of potent anti-malarial agents. Brain endothelial cell activation and dysfunction from oxidative and inflammatory host responses and products released by Plasmodium falciparum-infected erythrocytes (IE), are likely the major contributors to the encephalopathy, seizures, and brain swelling that are associated with CM. The development of adjunctive therapy to reduce the pathological consequences of host response pathways could improve outcomes. A potentially protective role of the nuclear factor E2-related factor 2 (NRF2) pathway, which serves as a therapeutic target in brain microvascular diseases and central nervous system (CNS) inflammatory diseases such as multiple sclerosis was tested to protect endothelial cells in an in vitro culture system subjected to tumour necrosis factor (TNF) or infected red blood cell exposure. NRF2 is a transcription factor that mediates anti-oxidant and anti-inflammatory responses.

Not Open Access | Nanotized curcumin-benzothiophene conjugate: A potential combination for treatment of cerebral malaria

October 13, 2020 - 12:50 -- NOT Open Access
Author(s): 
Ghosh A, Banerjee T
Reference: 
IUBMB Life. 2020 Oct 9.

The declining effectiveness of the available antimalarial drugs due to drug resistance requires a continued effort to develop new therapeutic approaches. In this context, combination therapies hold a great promise for developing effective first-line antimalarial treatments for reducing malaria mortality. The present study explores the antimalarial efficacy of nanotized formulation of curcumin in combination with benzothiophene compound 6 (3-bromo-N-(4-fluorobenzyl)-benzo[b]thiophene-2-carboxamide) with a view to achieve better efficacy at a very low dose in comparison to that accomplished with monotherapy alone.

Bisphosphoglycerate Mutase Deficiency Protects against Cerebral Malaria and Severe Malaria-Induced Anemia

September 24, 2020 - 08:15 -- Open Access
Author(s): 
Xu G, van Bruggen R, Gros P, et al.
Reference: 
Cell Rep. 2020 Sep 22;32(12):108170

The replication cycle and pathogenesis of the Plasmodium malarial parasite involves rapid expansion in red blood cells (RBCs), and variants of certain RBC-specific proteins protect against malaria in humans. In RBCs, bisphosphoglycerate mutase (BPGM) acts as a key allosteric regulator of hemoglobin/oxyhemoglobin. We demonstrate here that a loss-of-function mutation in the murine Bpgm (BpgmL166P) gene confers protection against both Plasmodium-induced cerebral malaria and blood-stage malaria.

NOT Open Access | Blood-cerebrospinal fluid barrier: another site disrupted during experimental cerebral malaria caused by Plasmodium berghei ANKA

September 8, 2020 - 11:42 -- NOT Open Access
Author(s): 
Ngo-Thanh H, Sasaki T, Suzue K, Yokoo H, Isoda K, Kamitani W, Shimokawa C, Hisaeda H, Imai T
Reference: 
Int J Parasitol. 2020 Aug 31:S0020-7519(20)30247-2

Cerebral malaria (CM) is one of the most severe pathologies of malaria; it induces neuro-cognitive sequelae and has a high mortality rate. Although many factors involved in the development of CM have been discovered, its pathogenic mechanisms are still not completely understood. Most studies on CM have focused on the blood-brain barrier (BBB), despite the importance of the blood-cerebrospinal fluid barrier (BCSFB), which protects the brain from peripheral inflammation.

How Does Blood-Retinal Barrier Breakdown Relate to Death and Disability in Pediatric Cerebral Malaria

August 27, 2020 - 08:21 -- Open Access
Author(s): 
MacCormick IJC, Barrera V, Beare NAV, Czanner G, Potchen M, Kampondeni S, Heyderman RS, Craig AG, Molyneux ME, Mallewa M, White VA, Milner D, Hiscott P, Taylor TE, Seydel KB, Harding SP
Reference: 
J Infect Dis. 2020 Aug 26:jiaa541

In cerebral malaria, the retina can be used to understand disease pathogenesis. The mechanisms linking sequestration, brain swelling and death remain poorly understood. We hypothesized that retinal vascular leakage would be associated with brain swelling.

Mesenchymal stromal cells protect against vascular damage and depression-like behavior in mice surviving cerebral malaria

August 27, 2020 - 08:15 -- Open Access
Author(s): 
Lima MN, Oliveira HA, Fagundes PM, Estato V, Silva AYO, Freitas RJRX, Passos BABR, Oliveira KS, Batista CN, Vallochi AL, Rocco PRM, Castro-Faria-Neto HC, Maron-Gutierrez T
Reference: 
Stem Cell Res Ther. 2020 Aug 26;11(1):367

Malaria is one of the most critical global infectious diseases. Severe systemic inflammatory diseases, such as cerebral malaria, lead to the development of cognitive and behavioral alterations, such as learning disabilities and loss of memory capacity, as well as increased anxiety and depression. The consequences are profound and usually contribute to reduce the patient's quality of life. There are no therapies to treat the neurological sequelae of cerebral malaria. Mesenchymal stromal cells (MSCs) may be an alternative, since they have been used as therapy for neurodegenerative diseases and traumatic lesions of the central nervous system. So far, no study has investigated the effects of MSC therapy on the blood-brain barrier, leukocyte rolling and adherence in the brain, and depression like-behavior in experimental cerebral malaria.

NOT Open Access | Aberrant Dopamine Receptor Signaling Plays Critical Role in the Impairment of Striatal Neurons in Experimental Cerebral Malaria

August 25, 2020 - 09:11 -- NOT Open Access
Author(s): 
Kumar SP, Babu PP
Reference: 
Mol Neurobiol. 2020 Aug 24

One-fourth survivors of cerebral malaria (CM) retain long-term cognitive and behavioral deficits. Structural abnormalities in striatum are reported in 80% of children with CM. Dopamine receptors (D1 and D2) are widely expressed in striatal medium spiny neurons (MSNs) that regulate critical physiological functions related to behavior and cognition. Dysregulation of dopamine receptors alters the expression of downstream proteins such as dopamine- and cAMP-regulated phosphoprotein (DARPP), Ca2+/calmodulin-dependent protein kinase II alpha (CaMKIIα), and p25/cyclin-dependent kinase 5 (cdk5).

NOT Open Access | Serum levels of Total human Tau associated with axonal damage among severe malaria patients in Central India

August 25, 2020 - 08:54 -- NOT Open Access
Author(s): 
Jain V, Thomas T, Basak S, Sharma RK, Singh N
Reference: 
Acta Trop. 2020 Aug 20:105675

Tau is a microtubule-associated protein (MAP) that is abundant in the axonal part of neurons of the central nervous system. Previous studies among African children and Vietnamese adults suffering from cerebral malaria (CM) showed the pathological significance of measuring circulatory total Tau levels. A pilot investigation was carried out to better characterise neurological pathogenesis among severe malaria patients in Central India.

Aminoquinolines affording resistance to cerebral malaria of susceptible mice

August 19, 2020 - 16:05 -- Open Access
Author(s): 
Srbljanović J, Bobić B, Štajner T, Uzelac A, Opsenica I, Terzić-Jovanović N, Bauman N, Šolaja BA, Djurković-Djaković O
Reference: 
J Glob Antimicrob Resist. 2020 Aug 15:S2213-7165(20)30202-2

Malaria treatment is impeded by growing resistance to conventional drugs. We here explore the activity of 10 novel benzothiophene, thiophene and benzene aminoquinolines.

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