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cerebral malaria

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.

Testing the impact of a single nucleotide polymorphism in a Plasmodium berghei ApiAP2 transcription factor on experimental cerebral malaria in mice

August 18, 2020 - 14:43 -- Open Access
Author(s): 
Akkaya M, Bansal A, Sheehan PW, Pena M, Cimperman CK, Qi CF, Yazew T, Otto TD, Billker O, Miller LH, Pierce SK
Reference: 
Sci Rep. 2020 Aug 12;10(1):13630

Cerebral malaria (CM) is the deadliest form of severe Plasmodium infections. Currently, we have limited understanding of the mechanisms by which Plasmodium parasites induce CM. The mouse model of CM, experimental CM (ECM), induced by infection with the rodent parasite, Plasmodium berghei ANKA (PbANKA) has been extensively used to study the pathophysiology of CM. Recent genomic analyses revealed that the coding regions of PbANKA and the closely related Plasmodium berghei NK65 (PbNK65), that does not cause ECM, differ in only 21 single nucleotide polymorphysims (SNPs).

NOT Open Access | Synergistic effect of combined artesunate and tetramethylpyrazine in experimental cerebral malaria

August 17, 2020 - 13:11 -- NOT Open Access
Author(s): 
Jiang X, Chen L, Zheng Z, Chen Y, Weng X, Guo Y, Li K, Yang T, Qu S, Liu H, Li Y, Zhu X
Reference: 
ACS Infect Dis. 2020 Aug 12

Intravenous artesunate is effective against cerebral malaria (CM), but high mortality and neurological sequelae in survivors are inevitable. We investigated the effect of combined artesunate and tetramethylpyrazine using mouse models of cerebral malaria (ECM). Artesunate+tetramethylpyrazine reduced microvascular blockage and improved neurological function, including the rapid murine coma and behavior scale (RMCBS), leading to improved survival and reduced pathology in ECM.

Not Open Access | RTP4 inhibits IFN-I response and enhances experimental cerebral malaria and neuropathology

July 27, 2020 - 14:58 -- NOT Open Access
Author(s): 
He X, Ashbrook AW, Su XZ, et al.
Reference: 
Proc Natl Acad Sci U S A. 2020 Jul 24:202006492

Infection by malaria parasites triggers dynamic immune responses leading to diverse symptoms and pathologies; however, the molecular mechanisms responsible for these reactions are largely unknown. We performed Trans-species Expression Quantitative Trait Locus analysis to identify a large number of host genes that respond to malaria parasite infections. Here we functionally characterize one of the host genes called receptor transporter protein 4 (RTP4) in responses to malaria parasite and virus infections.

Pathophysiology and neurologic sequelae of cerebral malaria

July 27, 2020 - 12:07 -- Open Access
Author(s): 
Nicoline Schiess, Andres Villabona-Rueda, Karissa E. Cottier, Katherine Huether, James Chipeta and Monique F. Stins
Reference: 
Malaria Journal 2020 19:266, 23 July 2020

Cerebral malaria (CM), results from Plasmodium falciparum infection, and has a high mortality rate. CM survivors can retain life-long post CM sequelae, including seizures and neurocognitive deficits profoundly affecting their quality of life. As the Plasmodium parasite does not enter the brain, but resides inside erythrocytes and are confined to the lumen of the brain’s vasculature, the neuropathogenesis leading to these neurologic sequelae is unclear and under-investigated.

Parasite histones are toxic to brain endothelium and link blood barrier breakdown and thrombosis in cerebral malaria

July 15, 2020 - 14:22 -- Open Access
Author(s): 
Moxon CA, Alhamdi Y, Storm J, Toh CH, et al.
Reference: 
Blood Adv. 2020 Jul 14; 4(13):2851-2864

Microvascular thrombosis and blood-brain barrier (BBB) breakdown are key components of cerebral malaria (CM) pathogenesis in African children and are implicated in fatal brain swelling. How Plasmodium falciparum infection causes this endothelial disruption and why this occurs, particularly in the brain, is not fully understood. In this study, we have demonstrated that circulating extracellular histones, equally of host and parasite origin, are significantly elevated in CM patients. Higher histone levels are associated with brain swelling on magnetic resonance imaging.

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