Cerebral Malaria Causes Enduring Behavioral and Molecular Changes in Mice Brain Without Causing Gross Histopathological Damage

Souza, Thaíze Lopes de; Grauncke, Ana Claudia Beck; Ribeiro, Leandro Rodrigo; Mello, Fernanda Kulinski; Oliveira, Sara Marchesan; Brant, Fátima; Machado, Fabiana S.; Oliveira, Mauro Schneider

doi:10.1016/j.neuroscience.2017.10.043

Cited by 15 publications

(16 citation statements)

References 48 publications

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“…S2A). At the same time, malaria infection also resulted in a marked loss of body weight in experimental animals in line with previous studies 34,36 . DHA treatment halted further weight loss until the end of the experiment (Fig.…”

Section: Resultssupporting

confidence: 91%

A retinal model of cerebral malaria

Paquet-Durand

Beck

Das

et al. 2019

Sci Rep

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Malaria is a causative factor in about 500.000 deaths each year world-wide. Cerebral malaria is a particularly severe complication of this disease and thus associated with an exceedingly high mortality. Malaria retinopathy is an ocular manifestation often associated with cerebral malaria, and presumably shares a substantial part of its pathophysiology. Here, we describe that indeed murine malaria retinopathy reproduced the main hallmarks of the corresponding human disease. In the living animal, we were able to follow the circulation and cellular localization of malaria parasites transgenically labelled with GFP via non-invasive in vivo retinal imaging. We found that malaria parasites cross the blood-retinal-barrier and infiltrate the neuroretina, concomitant with an extensive, irreversible, and long-lasting retinal neurodegeneration. Furthermore, anti-malarial treatment with dihydroartemisinin strongly diminished the load of circulating parasites but resolved the symptoms of the retinopathy only in part. In summary, we introduce here a novel preclinical model for human cerebral malaria that is much more directly accessible for studies into disease pathophysiology and development of novel treatment approaches. In vivo retinal imaging may furthermore serve as a valuable tool for the early diagnosis of the human disease.

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Section: Resultssupporting

confidence: 91%

A retinal model of cerebral malaria

Paquet-Durand

Beck

Das

et al. 2019

Sci Rep

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“…Statistical analysis of parasitaemia in the three groups, done up to the seventh day because by day eight most of the C57BL/6 mice had died, did not present significant differences (p=0.895). Similar results were reported in assays with C57BL/6 mice, however, 24,12,25 parasitaemias higher than 80% have also been reported for this strain by the 14th day post infection. 26 As for the BALB/c mice parasitaemia, distinct results have been reported, with increases and decreases throughout the course of infection, even reporting hyperparasitaemias.…”

Section: Resultssupporting

confidence: 88%

Evaluation of malaria pathology development in a group of CB6F1 mice produced in the laboratory animal facilities of INDICASAT AIP

Jesús¹,

Spadafora²

2018

MOJBB

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The purpose of this assay was to characterize the infection by Plasmodium berghei of three groups of inbred mice to determine which group is more appropriate to use as a biomodel for testing ethnobotanical anti-malarial compounds. A group of mice, CB6F1 (BALB/c x C57BL/6), and two inbred strains of mice, C57BL/6 and BALB/c, were parasitized with P. berghei (ANKA) and were evaluated as to average weight, behavioral parameters and integrity of the Brain Blood Barrier. These data were correlated to their parasitaemia. In reference to the average weight, all of the animals in the three groups lost weight as the infection progressed. This decrease did not present significant differences between the individual animals of the group (p=0.8841). When correlating the four stages to the evolution of malaria, Stages III and IV of disease progression correlated to the manifestation of cerebral malaria, verified by the presence of injury to the Brain Blood Barrier. Thirtyseven percent of the CB6F1 mice showed signs of Stage IV, and 63% showed signs of Stage III, both with a median parasitaemia of 24±2,7%. One hundred percent of C57BL/6 mice presented Stage III, with a median parasitaemia of 28%, while the BALB/c showed no clinical manifestations of cerebral malaria, in spite of parasitaemias as high as 60% at the time of death. The tests revealed that strain C57BL/6 is more appropriate to use as a biomodel for testing ethnobotanical anti-malarial compounds.

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“…The pathophysiology of CM involves a range of cellular and histological processes, including cell sequestration, brain inflammation and the breakdown of the blood-brain barrier that can discharge major impairments in the behavior of infected animals [ 36 ]. The murine model of CM is a valuable tool to the development of effective treatments, given that mice reproduce most of the symptoms observed in humans [ 37 ]. In the present study, PbA-infected mice presented a number of symptoms characteristic of human cerebral malaria, including ataxia, poor reflexes, seizures and coma [ 36 ].…”

Section: Discussionmentioning

confidence: 99%

Euterpe oleracea fruit (Açai)-enriched diet suppresses the development of experimental cerebral malaria induced by Plasmodium berghei (ANKA) infection

Oliveira¹,

Torres²,

Kauffmann³

et al. 2022

BMC Complement Med Ther

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Background Cerebral malaria is one of the most severe complications attributed to protozoal infection by Plasmodium falciparum, gaining prominence in children mortality rates in endemic areas. This condition has a complex pathogenesis associated with behavioral, cognitive and motor sequels in humans and current antimalarial therapies have shown little effect in those aspects. Natural products with antioxidant and anti-inflammatory properties have become a valuable alternative therapeutic option in the treatment of distinct conditions. In this context, this study investigated the neuroprotective effect of Euterpe oleracea (açai) enriched diet during the development of experimental cerebral malaria induced by the inoculation of Swiss albino mice with Plasmodium berghei ANKA strain. Methods After Plasmodium infection, animals were maintained on a feeding with Euterpe oleracea enriched ration and parameters such as survival curve, parasitemia and body weight were routinely monitored. The present study has also evaluated the effect of açai-enriched diet on the blood-brain barrier leakage, histological alterations and neurocognitive impairments in mice developing cerebral malaria. Results Our results demonstrate that between 7th–19th day post infection the survival rate of the group treated with açai enriched ration was higher when compared with Plasmodium-infected mice in which 100% of mice died until the 11th days post-infection, demonstrating that açai diet has a protective effect on the survival of infected treated animals. The same was observed in the brain vascular extravasation, where Evans blue dye assays showed significantly less dye extravasation in the brains of Plasmodium-infected mice treated with açai enriched ration, demonstrating more preserved blood-brain barrier integrity. Açai-enriched diet also attenuate the histopathological alterations elicited by Plasmodium berghei infection. We also showed a decrease of the neurological impairments arising from the exposure of cerebral parenchyma in the group treated with açai diet, ameliorating motor and neuropsychiatric changes, analyzed through the SHIRPA protocol. Conclusion With these results, we conclude that the treatment with açai enriched ration decreased the mortality of infected animals, as well as protected the blood-brain barrier and the neurocognitive deficits in Plasmodium-infected animals.

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Cerebral Malaria Causes Enduring Behavioral and Molecular Changes in Mice Brain Without Causing Gross Histopathological Damage

Cited by 15 publications

References 48 publications

A retinal model of cerebral malaria

A retinal model of cerebral malaria

Evaluation of malaria pathology development in a group of CB6F1 mice produced in the laboratory animal facilities of INDICASAT AIP

Euterpe oleracea fruit (Açai)-enriched diet suppresses the development of experimental cerebral malaria induced by Plasmodium berghei (ANKA) infection

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