Artesunate and erythropoietin synergistically improve the outcome of experimental cerebral malaria

Du, Yunting; Chen, Guang; Zhang, Xuexing; Yu, Chunyun; Cao, Yaming

doi:10.1016/j.intimp.2017.05.008

Cited by 20 publications

(17 citation statements)

References 53 publications

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“…Previous studies have suggested that the artesunate can regulate Th cells in virus infections. Du and colleagues ( 123 ) demonstrated that the artesunate downregulated the Th1 response and reduced levels of IFN-γ, TNF-α, IL-12, IL-18, CCL2, CXCL9, and CXCL10 in an experimental model of cerebral malaria. RA is an autoimmune disease manifested by dysfunction of various immune cells (e.g., APCs, Th1, Th17), which leads to a high concentration of IL-1, IL-6, TNF-α, and chemokines in plasma and tissues ( 124 ).…”

Section: Potential Treatments For Cytokine Storm In Covid-19 and Theimentioning

confidence: 99%

Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies

et al. 2020

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Severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2) is the pathogen that causes coronavirus disease 2019 (COVID-19). As of 25 May 2020, the outbreak of COVID-19 has caused 347,192 deaths around the world. The current evidence showed that severely ill patients tend to have a high concentration of pro-inflammatory cytokines, such as interleukin (IL)-6, compared to those who are moderately ill. The high level of cytokines also indicates a poor prognosis in COVID-19. Besides, excessive infiltration of pro-inflammatory cells, mainly involving macrophages and T-helper 17 cells, has been found in lung tissues of patients with COVID-19 by postmortem examination. Recently, increasing studies indicate that the “cytokine storm” may contribute to the mortality of COVID-19. Here, we summarize the clinical and pathologic features of the cytokine storm in COVID-19. Our review shows that SARS-Cov-2 selectively induces a high level of IL-6 and results in the exhaustion of lymphocytes. The current evidence indicates that tocilizumab, an IL-6 inhibitor, is relatively effective and safe. Besides, corticosteroids, programmed cell death protein (PD)-1/PD-L1 checkpoint inhibition, cytokine-adsorption devices, intravenous immunoglobulin, and antimalarial agents could be potentially useful and reliable approaches to counteract cytokine storm in COVID-19 patients.

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Section: Potential Treatments For Cytokine Storm In Covid-19 and Theimentioning

confidence: 99%

Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies

et al. 2020

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“…Erythropoietin, a hormone produced by the kidneys, has been considered for use in CM as also has antioxidant and anti-inflammatory components in animal models. Murine studies have demonstrated positive, neuroprotective results, either alone [ 147 ] or when paired with artesunate [ 148 ]. However, clinical studies demonstrated that high erythropoietin levels are associated with extended coma and increased mortality [ 149 ].…”

Section: Introductionmentioning

confidence: 99%

Pathophysiology and neurologic sequelae of cerebral malaria

Schiess¹,

Villabona-Rueda

Cottier

et al. 2020

Malar J

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Cerebral malaria (CM), results from Plasmodium falciparum infection, and has a high mortality rate. CM survivors can retain lifelong 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 underinvestigated. Interestingly, postmortem CM pathology differs in brain regions, such as the appearance of haemorragic punctae in white versus gray matter. Various host and parasite factors contribute to the risk of CM, including exposure at a young age, parasite-and host-related genetics, parasite sequestration and the extent of host inflammatory responses. Thus far, several proposed adjunctive treatments have not been successful in the treatment of CM but are highly needed. The region-specific CM neuro-pathogenesis leading to neurologic sequelae is intriguing, but not sufficiently addressed in research. More attention to this may lead to the development of effective adjunctive treatments to address CM neurologic sequelae.

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“…Immunohistochemical staining was performed with specific polyclonal antibodies against intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), glial fibrillary acidic protein (GFAP) and neuron-specific nuclear protein (NeuN) to detect the protein expression. Vessels were counted in 20 randomly selected fields per mouse using the method described in the literature [21]. GFAP-immunopositive cells in the cerebral cortex and NeuN-immunopositive cells in the hippocampus were quantified in each mouse brain and counted in five areas per section.…”

Section: Methodsmentioning

confidence: 99%

Powerful solution for experimental cerebral malaria treatment: artesunate and tetramethylpyrazine

Jiang

Chen

Zheng

et al. 2019

Preprint

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BackgroundCerebral malaria (CM) is a kind of serious neurological complication caused by the acute Plasmodium falciparum infection. About 300000 patients including children under 5 years old died from this disease every year. Even intravenous artesunate (Art) is employed as the most effictive drug in the treatment of CM, high incidence of death and neurological sequelae are still inevitable. Therefore, we assessed the combination of Art and tetramethylpyrazine (TMP), to treat experimental CM (ECM) in C57BL/6 mice infected with Plasmodium berghei ANKA (PbA). A non-biased whole brain quantitative proteomic analysis was also conducted to get some insight of the mechanism of the combinational treatment.ResultsTreatment of (ECM)-C57BL/6 mice with the combination of Art and TMP increased the survival, improved clinical signs and prevented neurological manifestations. These effects were related to reduction of parasitised red blood cells (pRBC) adhesion, sequestration, maintaining brain microvascular integrity, increasing nerve growth factor, neurotrophin levels, and alleviating hippocampal neuronal damage and astrocyte activation. The pharmacological effects of Art-TMP combination therapy were analyzed by ECM mice brain proteomic function enrichment. Based on an isobaric tag for relative and absolute quantitation (iTRAQ) fold-change of 1.2 (P-value < 0.05), 217 down-regulated and 177 up-regulated proteins were identified, presenting a significantly altered proteome profile of the combined Art and TMP group as compared to the group treated with Art or TMP alone. These results suggested that the Art-TMP combination could be used as a powerful solution for CM and its neurologic damage.ConclusionsAn effictive therapy for CM with low mortality rate and protect against ECM-induced neurocognitive impairment has been proposed through the combination of Art and TMP, which can provide an effective adjuvant treatment in the clinic. iTRAQ proteomics provide a resource for further mechanistic studies to examine the synergistic effects of Art and TMP and their potential to serve as an adjunctive treatment method and intervention targets.Author SummaryCerebral malaria (CM) is the most serious neurological complication caused by Plasmodium falciparum infection. Even after antimalarial treatment, severe neurological sequelae still exist. We used tetramethylpyrazine (TMP), the main ingredient of the traditional Chinese medicine Chuanxiong, and artesunate (Art) as a combination of drugs. We found that Art-TMP combination could improve the clinical symptoms of CM and protect the nervous system. At the same time, proteomics was used to analyze the protective mechanism of Art-TMP combination administration on ECM mice. This study suggests that the combination of Art and TMP may be used as an adjuvant therapy for clinical CM and iTRAQ proteomics provides resources for further study of Art-TMP combination and provides potential prognostic biomarkers for this therapeutic intervention.

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Artesunate and erythropoietin synergistically improve the outcome of experimental cerebral malaria

Cited by 20 publications

References 53 publications

Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies

Cytokine Storm in COVID-19: The Current Evidence and Treatment Strategies

Pathophysiology and neurologic sequelae of cerebral malaria

Powerful solution for experimental cerebral malaria treatment: artesunate and tetramethylpyrazine

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