Manifestation of Cerebral Malaria-like Symptoms in the WM/Ms Rat Infected with Plasmodium berghei Strain NK65

Kamiyama, Tsuneo; Tatsumi, Masashi; Matsubara, Junko; Yamamoto, Katsunobu; Rubio, Zuleima; Cortes, Gladys; Fujii, Hiroki

doi:10.2307/3282294

Cited by 15 publications

(4 citation statements)

References 10 publications

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“…However, this parasite did cause BBB breakdown in the 3 week-old CBA/CaJ mice used here. The PbNK-induced ECM susceptibility may be age-related, since young, but not older, rats were also reported to develop a neurological syndrome [47]. None of the PyXL- or PyYM-infected mice examined here exhibited any evidence for neurological impairment or vascular leakage despite HP and consequently exposure of the cerebral microvasculature to significantly larger numbers of iRBC compared to PbA- or PbNK-infected mice that did develop ECM.…”

Section: Discussionmentioning

confidence: 73%

Neuroimmunological Blood Brain Barrier Opening in Experimental Cerebral Malaria

et al. 2012

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Plasmodium falciparum malaria is responsible for nearly one million annual deaths worldwide. Because of the difficulty in monitoring the pathogenesis of cerebral malaria in humans, we conducted a study in various mouse models to better understand disease progression in experimental cerebral malaria (ECM). We compared the effect on the integrity of the blood brain barrier (BBB) and the histopathology of the brain of P. berghei ANKA, a known ECM model, P. berghei NK65, generally thought not to induce ECM, P. yoelii 17XL, originally reported to induce human cerebral malaria-like histopathology, and P. yoelii YM. As expected, P. berghei ANKA infection caused neurological signs, cerebral hemorrhages, and BBB dysfunction in CBA/CaJ and Swiss Webster mice, while Balb/c and A/J mice were resistant. Surprisingly, PbNK induced ECM in CBA/CaJ mice, while all other mice were resistant. P. yoelii 17XL and P. yoelii YM caused lethal hyperparasitemia in all mouse strains; histopathological alterations, BBB dysfunction, or neurological signs were not observed. Intravital imaging revealed that infected erythrocytes containing mature parasites passed slowly through capillaries making intimate contact with the endothelium, but did not arrest. Except for relatively rare microhemorrhages, mice with ECM presented no obvious histopathological alterations that would explain the widespread disruption of the BBB. Intravital imaging did reveal, however, that postcapillary venules, but not capillaries or arterioles, from mice with ECM, but not hyperparasitemia, exhibit platelet marginalization, extravascular fibrin deposition, CD14 expression, and extensive vascular leakage. Blockage of LFA-1 mediated cellular interactions prevented leukocyte adhesion, vascular leakage, neurological signs, and death from ECM. The endothelial barrier-stabilizing mediators imatinib and FTY720 inhibited vascular leakage and neurological signs and prolonged survival to ECM. Thus, it appears that neurological signs and coma in ECM are due to regulated opening of paracellular-junctional and transcellular-vesicular fluid transport pathways at the neuroimmunological BBB.

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Section: Discussionmentioning

confidence: 73%

Neuroimmunological Blood Brain Barrier Opening in Experimental Cerebral Malaria

et al. 2012

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“…For example, why do certain reticulocyte-tropic Plasmodium species such as PbA, Pb K173, and less frequently also P. berghei NK65 [86, 195], induce ECM in some susceptible mouse or rat strains, but not in others (reviewed in [136])? Further, do iRBC, in particular P. vivax infected reticulocytes, travel through human brain capillaries at reduced velocity, similar to PbA iRBC during ECM [86]?…”

Section: Imaging Cerebral Malaria Pathogenesismentioning

confidence: 99%

Imaging Plasmodium immunobiology in the liver, brain, and lung

Frevert¹,

Nacer²,

Cabrera³

et al. 2014

Parasitology International

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Plasmodium falciparum malaria is responsible for the deaths of over half a million African children annually. Until a decade ago, dynamic analysis of the malaria parasite was limited to in vitro systems with the typical limitations associated with 2D monocultures or entirely artificial surfaces. Due to extremely low parasite densities, the liver was considered a black box in terms of Plasmodium sporozoite invasion, liver stage development, and merozoite release into the blood. Further, nothing was known about the behavior of blood stage parasites in organs such as brain where clinical signs manifest and the ensuing immune response of the host that may ultimately result in a fatal outcome. The advent of fluorescent parasites, advances in imaging technology, and availability of an ever-increasing number of cellular and molecular probes have helped illuminate many steps along the pathogenetic cascade of this deadly tropical parasite.

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“…P. chabaudi subsp. chabaudi AS was maintained by syringe passage every week in mice (20). PRBCs were collected by heart puncture, washed and suspended in phosphate-buffered saline (PBS).…”

Section: Methodsmentioning

confidence: 99%

Transforming Growth Factor β-Induced Failure of Resistance to Infection with Blood-StagePlasmodium chabaudiin Mice

Tsutsui

Kamiyama

1999

Infect Immun

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The role of transforming growth factor β (TGF-β) in infection with Plasmodium chabaudi was investigated with resistant and susceptible mouse models. C57BL/10 mice produced gamma interferon (IFN-γ) and nitric oxide (NO) shortly after infection and cleared the parasite spontaneously. In contrast, BALB/c mice showed a transient enhancement of TGF-β production, followed by a relative lack of IFN-γ and NO production, and succumbed to the infection. However, there was no correlation between levels of serum TGF-β and splenic TGF-β mRNA in both mouse strains before and after infection. Administration of recombinant TGF-β (rTGF-β) rendered resistant mice susceptible because of suppression of subsequent production of IFN-γ and NO. Administration of anti-TGF-β antibody to the infected BALB/c mice resulted in remarkable increases in serum IFN-γ and NO, and the mice resisted the infection. Splenic CD4+ T and CD11b+ cells of C57BL/10 mice were significantly activated after infection, but this was completely abrogated by administration of rTGF-β. These results suggested that, in the P. chabaudi-susceptible but not resistant mice, production of TGF-β was promoted, and subsequent failure of IFN-γ- and NO-dependent resistance to the parasite was induced. This study is the first to indicate that TGF-β production was the key event in failure of resistance to mouse malaria.

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Manifestation of Cerebral Malaria-like Symptoms in the WM/Ms Rat Infected with Plasmodium berghei Strain NK65

Cited by 15 publications

References 10 publications

Neuroimmunological Blood Brain Barrier Opening in Experimental Cerebral Malaria

Neuroimmunological Blood Brain Barrier Opening in Experimental Cerebral Malaria

Imaging Plasmodium immunobiology in the liver, brain, and lung

Transforming Growth Factor β-Induced Failure of Resistance to Infection with Blood-StagePlasmodium chabaudiin Mice

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