Cytokine and chemokine responses in a cerebral malaria-susceptible or -resistant strain of mice to Plasmodium berghei ANKA infection: early chemokine expression in the brain

Abstract Cerebral malaria is a complication of Plasmodium falciparum infection and can cause death in humans. Plasmodium berghei ANKA (PbA) infection in C57BL/6 strain is widely used for cerebral malaria research. However, research to assess differences in brain histopathology, TNFα levels and the degree of parasitemia in Swiss websters infected with PbA are still limited. Therefore an infection with P. berghei ANKA strain was carried out on Swiss webster mice and C57BL/6 as a model of cerebral malaria. This research is a laboratory experiment with a post-test only control group design. Each experimental animal was divided into 3 groups namely PbA group (infected and given aquades), DHP (infected and given Dihidroartemisinin piperakuin), and healthy (mice not infected with PbA called aquades). Animal testing tried to examine parasitemia by microscopic counts on thin blood smear, calculation of serum TNFα levels by ELISA method and histopathology of the brain and slide microscopic examination with Haematoxylin Eosin staining conducted at the Experimental Animal Laboratory, Parasite Laboratory, Puslitbang BTDK, NIHRD; and Balitvet Pathology Laboratory by the research team. The results showed a peak percentage of parasitemia in the PbA group on day 4 for the Swiss webster strain (68.8%) and on the 5th day for the C57BL/6 strain (43.7%). The percentage of parasitemia was higher in the Swiss webster strain than in the C57BL/6 strain. TNFα levels in the Swiss webster strain (3.6 pg/ml) were higher than TNFα levels in the C57BL/6 strain (0.18 pg/ml). Histopathological changes in the brain consisting of lymphocyte cells, infiltration, macrophages, gliosis, necrosis, vacuolization and malaria parasitemia were found in both strains. The results showed that Swiss webster mice can be used as a model of cerebral malaria when seen from the clinical picture, the percentage of parasitemia, serum TNFα levels, macroscopic and microscopic brains that have similarities to the C57BL/6 strain. Keywords: Cerebral malaria, Plasmodium berghei ANKA, Swiss webster, C57BL/6. Abstrak Malaria serebral merupakan salah satu komplikasi infeksi Plasmodium falciparum dan dapat menyebabkan kematian pada manusia. Infeksi Plasmodium berghei ANKA (PbA) pada mencit galur C57BL/6 banyak digunakan untuk penelitian malaria serebral. Di Indonesia, mencit Swiss webster banyak digunakan sebagai hewan coba untuk malaria, namun penelitian untuk menilai perbedaaan histopatologi otak, kadar TNFα dan derajat parasitemia pada Swiss webster yang diinfeksi PbA masih terbatas. Oleh sebab itu dilakukan infeksi P. berghei galur ANKA pada mencit Swiss webster dan C57BL/6 sebagai model malaria serebral. Penelitian ini merupakan eksperimen laboratorium dengan desain post-test only control group. Masing-masing galur hewan coba dibagi menjadi 3 kelompok yaitu kelompok PbA (diinfeksi dan diberi akuades), DHP (diinfeksi dan diberi Dihidroartemisinin piperakuin), dan sehat (mencit yang tidak diinfeksi PbA yang diberi akuades). Pengujian pada hewan coba meliputi pemeriksaan parasitemia dengan penghitungan kepadatan parasit secara mikroskopis pada ulas darah tipis, penghitungan kadar TNFα serum dengan metode ELISA serta gambaran histopatologi sediaan otak dengan pewarnaan Haematoksilin Eosin dilakukan di Laboratorium Hewan Coba, Laboratorium Parasit Puslitbang BTDK, Badan Litbangkes; dan Laboratorium Patologi Balitvet oleh tim peneliti. Hasil penelitian menunjukkan puncak persentase parasitemia kelompok PbA pada hari ke- 4 untuk galur Swiss webster (68.8%) sementara untuk galur C57BL/6 (43.7%) pada hari ke-5. Hal ini berarti bahwa puncak parasitemia lebih cepat dan tinggi terjadi pada galur Swiss webster dibandingkan pada galur C57BL/6. Demikian juga untuk kadar TNFα didapatkan bahwa pada galur Swiss webster (3.6 pg/ml) lebih tinggi dibandingkan galur C57BL/6 (0.18 pg/ml). Perubahan histopatologik otak berupa infiltrasi sel limfosit, makrofag, gliosis, nekrosis, vakuolisasi dan parasitemia malaria ditemukan pada kedua galur. Hasil penelitian menunjukkan bahwa mencit galur Swiss webster dapat dijadikan sebagai model malaria serebral. Kata kunci: Malaria serebral, Plasmodium berghei ANKA, Swiss webster, C57BL/6.

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Ginger Extract Has An Ability To Safe C57BL / 6-WT Mice From Cerebral Malaria Produced By Plasmodium Berghei ANKA

10.37376/1571-000-059-008 ◽

2018 ◽

pp. 1

Author(s):

سالم رمضان على السريتى ◽

نوارة امراجع الازيرق العمارى

Keyword(s):

Cerebral Malaria ◽

Plasmodium Berghei ◽

Plasmodium Berghei Anka ◽

Ginger Extract

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Effects of endotoxin and dexamethasone on cerebral malaria in mice

Parasitology ◽

10.1017/s003118200006594x ◽

1995 ◽

Vol 111 (4) ◽

pp. 443-454 ◽

Cited By ~ 18

Author(s):

A. L. Neill ◽

N. H. Hunt

Keyword(s):

Cerebral Malaria ◽

Evans Blue ◽

Plasmodium Berghei ◽

Tumour Necrosis ◽

Brain Parenchyma ◽

Post Inoculation ◽

Cba Mice ◽

Cerebral Involvement ◽

The Brain ◽

Necrosis Factor

SUMMARYCBA/T6 and DBA/2J mice inoculated withPlasmodium bergheiANKA (PbA) develop cerebral involvement 6–8 days post-inoculation, from which the CBA mice almost invariably die and the DBA mice recover. Dexamethasone (DXM; 80 mg/kg) given to inoculated CBA mice twice, on day 3 and again within 48 h, reduced the cerebral symptoms and prevented death from cerebral malaria. Plasma tumour necrosis factor (TNF) levels, which increased at the time of the cerebral symptoms, were also reduced in these DXM-treated mice. Intravenously administered Evans Blue, a dye which binds to albumin, diffused extensively across the blood-brain barrier only during the period of cerebral symptoms, in proportion to the severity of the cerebral symptoms and the disease. In PbA-infected CBA mice, cerebral symptoms and the amount of Evans Blue diffusing into the brain tissue were both reduced by DXM treatment, but only if the steroid was given on day 3 and again within 48 h. Endotoxin injected intravascularly into PbA-infected DBA mice after day 5 resulted in an exaggeration of cerebral symptoms and death between days 6 and 9. Plasma TNF and the amount of Evans Blue in the brain parenchyma increased above normal levels in these mice. Endotoxin injections had only minor effects on the severity of the cerebral symptoms in PbA-infected CBA mice and did not cause the animals to die sooner.

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Early Perturbations in Glucose Utilization in Malaria-Infected Murine Erythrocytes, Liver and Brain Observed by Metabolomics

Metabolites ◽

10.3390/metabo10070277 ◽

2020 ◽

Vol 10 (7) ◽

pp. 277

Author(s):

Arjun Sengupta ◽

Soumita Ghosh ◽

Shobhona Sharma ◽

Haripalsingh M. Sonawat

Keyword(s):

Plasmodium Berghei ◽

Metabolic Pathways ◽

Malaria Parasite ◽

Glucose Utilization ◽

Early Infection ◽

Flux Analysis ◽

Plasmodium Berghei Anka ◽

Central Carbon ◽

The Brain ◽

Pathway Level

Investigation of glucose utilization during an infection is central to the study of energy metabolism. The heavy utilization of glucose by the malaria parasite, and the consequences of this process, have been investigated extensively. However, host glucose utilization during early infection has not been explored to date. In a first attempt, this article investigates the changes in the host glucose utilization in Balb/c mice infected with Plasmodium berghei ANKA using 13C-labeled glucose infusion followed by NMR spectroscopy. The results suggested significant alterations of liver, brain and red blood cell (RBC) glucose utilization during early infection when the parasitemia was <1%. At the pathway level, we observed a decrease in the shunt metabolite 2,3-bisphosphoglycerate in the RBCs. Glycolysis and pathways associated with it, along with fatty acid unsaturation, were altered in the liver. Significant changes were observed in the central carbon metabolic pathways in the brain. These results have implications in understanding the host physiology during early infection and pave the way for detailed flux analysis of the proposed perturbed pathways.

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