Magnetic Resonance Imaging of the Brain in Patients with Cerebral Malaria

Looareesuwan, S; Wilairatana, Polrat; Krishna, Sanjeev; Kendall, B. E.; Vannaphan, Suparp; Viravan, C; White, Nicholas J.

doi:10.1093/clinids/21.2.300

Cited by 122 publications

(69 citation statements)

References 21 publications

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“…Noninvasive MRI and MRA were used to follow the neuropathology caused by PbA infection, as in human patients to study brain changes during ECM (21)(22)(23)(24)(25). In ECM, MRI and MRA allow a semiquantitative analysis of edema/swelling, focal ischemia, morphological changes, and vascular blood flow (21,26).…”

Section: Reduced Cerebral Ischemia and Blood Flow Perturbation In Thementioning

confidence: 99%

IL-12Rβ2 Is Essential for the Development of Experimental Cerebral Malaria

Fauconnier

Palomo

Bourigault

et al. 2012

The Journal of Immunology

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A Th1 response is required for the development of Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM). The role of pro-Th1 IL-12 in malaria is complex and controversial. In this study, we addressed the role of IL-12Rβ2 in ECM development. C57BL/6 mice deficient for IL-12Rβ2, IL-12p40, or IL-12p35 were analyzed for ECM development after blood-stage PbA infection in terms of ischemia and blood flow by noninvasive magnetic resonance imaging and angiography, T cell recruitment, and gene expression. Without IL-12Rβ2, no neurologic sign of ECM developed upon PbA infection. Although wild-type mice developed distinct brain microvascular pathology, ECM-resistant, IL-12Rβ2–deficient mice showed unaltered cerebral microcirculation and the absence of ischemia after PbA infection. In contrast, mice deficient for IL-12p40 or IL-12p35 were sensitive to ECM development. The resistance of IL-12Rβ2–deficient mice to ECM correlated with reduced recruitment of activated T cells and impaired overexpression of lymphotoxin-α, TNF-α, and IFN-γ in the brain after PbA infection. Therefore, IL-12Rβ2 signaling is essential for ECM development but independent from IL-12p40 and IL-12p35. We document a novel link between IL-12Rβ2 and lymphotoxin-α, TNF-α, and IFN-γ expression, key cytokines for ECM pathogenesis.

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Section: Reduced Cerebral Ischemia and Blood Flow Perturbation In Thementioning

confidence: 99%

IL-12Rβ2 Is Essential for the Development of Experimental Cerebral Malaria

Fauconnier

Palomo

Bourigault

et al. 2012

The Journal of Immunology

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“…These noninvasive techniques enable investigation of neurologic disease and are used in human beings to study brain changes during CM. [21][22][23][24][25] In murine experimental CM, MRI and MRA enable semiquantitative analysis of swelling and edema, focal ischemia, morphologic changes, and vascular blood flow. This could be indicative of mi- Figure 1.…”

Section: Reduced Cerebral Ischemia By Noninvasive Imaging In Absence mentioning

confidence: 99%

Protein Kinase C-Theta Is Required for Development of Experimental Cerebral Malaria

Fauconnier

Bourigault

Même

et al. 2011

The American Journal of Pathology

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Cerebral malaria is the most severe neurologic complication in children and young adults infected with Plasmodium falciparum. T-cell activation is required for development of Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (CM). To characterize the T-cell activation pathway involved, the role of protein kinase C-theta (PKC-) in experimental CM development was examined. PKC--deficient mice are resistant to CM development. In the absence of PKC-, no neurologic sign of CM developed after blood stage PbA infection. Resistance of PKC--deficient mice correlated with unaltered cerebral microcirculation and absence of ischemia, as documented by magnetic resonance imaging and magnetic resonance angiography, whereas wild-type mice developed distinct microvascular pathology. Recruitment and activation of CD8 ؉ T cells, and ICAM-1 and CD69 expression were reduced in the brain of resistant mice; however, the pulmonary inflammation and edema associated with PbA infection were still present in the absence of functional PKC-. Resistant PKC--deficient mice developed high parasitemia, and died at 3 weeks with severe anemia. Therefore, PKC-signaling is crucial for recruitment of CD8 ؉ T cells and development of brain microvascular pathology resulting in fatal experimental CM, and may represent a novel therapeutic target of CM.

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“…CT scans of Kenyan children showed evidence of brain swelling which resolved during convalescence (Newton et al 1994) (Figure 2). Magnetic resonance imaging studies, which are even more sensitive, found little evidence of cerebral oedema in Thai adults (Looareesuwan et al 1995), but did find brain swelling. It is likely that increased cerebral blood volume (Newton et al 1991), from the sequestered mass and/or increased cerebral blood flow (Newton et al 1996) is responsible for the raised ICP in children.…”

Section: Studies Of the Functional Integritymentioning

confidence: 88%

Review Article: Blood-brain barrier in falciparum malaria*

Gitau

Newton

2005

Trop Med Int Health

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SummaryPlasmodium falciparum malaria is the most important parasitic disease infecting the central nervous system of humans worldwide. The pathogenesis of the neurological complications of falciparum malaria remains unclear. In particular, how do asexual parasites confined to the vascular space of the brain cause neuronal impairment? The evidence for a breakdown in the blood-brain barrier (BBB) is conflicting. In some animal models of malaria, there is evidence of breakdown of the BBB, but the data from humans suggests the BBB is mildly impaired only, with few morphological changes. Whether these changes in the BBB are sufficient to account for the neurological complications remains to be determined.keywords falciparum malaria, blood-brain barrier impairment

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Magnetic Resonance Imaging of the Brain in Patients with Cerebral Malaria

Cited by 122 publications

References 21 publications

IL-12Rβ2 Is Essential for the Development of Experimental Cerebral Malaria

IL-12Rβ2 Is Essential for the Development of Experimental Cerebral Malaria

Protein Kinase C-Theta Is Required for Development of Experimental Cerebral Malaria

Review Article: Blood-brain barrier in falciparum malaria*

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