Cerebral Malaria

Toro, Gerzaín Rodríguez

doi:10.1001/archneur.1978.00500290017004

Cited by 102 publications

(11 citation statements)

References 20 publications

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“…A compromised BBB likely contributes significantly to CM pathogenesis and pathology, and BBB damage increases as CM progresses towards its terminal stage [44]. In the optic nerve it was noted that a high level of axonal injury and demyelination was seen in perivascular regions [8]; similar to human CM [6,45]. Other types of neuropathology show a link between BBB breakdown and abnormal myelination [28,46].…”

Section: Discussionmentioning

confidence: 99%

Erythropoietin treatment alleviates ultrastructural myelin changes induced by murine cerebral malaria

Hempel

Hyttel

Staalsøe

et al. 2012

Malar J

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BackgroundCerebral malaria (CM) is a severe complication of malaria with considerable mortality. In addition to acute encephalopathy, survivors frequently suffer from neurological sequelae. The pathogenesis is incompletely understood, hampering the development of an effective, adjunctive therapy, which is not available at present. Previously, erythropoietin (EPO) was reported to significantly improve the survival and outcome in a murine CM model. The study objectives were to assess myelin thickness and ultrastructural morphology in the corpus callosum in murine CM and to adress the effects of EPO treatment in this context.MethodsThe study consisted of two groups of Plasmodium berghei-infected mice and two groups of uninfected controls that were either treated with EPO or placebo (n = 4 mice/group). In the terminal phase of murine CM the brains were removed and processed for electron microscopy. Myelin sheaths in the corpus callosum were analysed with transmission electron microscopy and stereology.ResultsThe infection caused clinical CM, which was counteracted by EPO. The total number of myelinated axons was identical in the four groups and mice with CM did not have reduced mean thickness of the myelin sheaths. Instead, CM mice had significantly increased numbers of abnormal myelin sheaths, whereas EPO-treated mice were indistinguishable from uninfected mice. Furthermore, mice with CM had frequent and severe axonal injury, pseudopodic endothelial cells, perivascular oedemas and intracerebral haemorrhages.ConclusionsEPO treatment reduced clinical signs of CM and reduced cerebral pathology. Murine CM does not reduce the general thickness of myelin sheaths in the corpus callosum.

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Section: Discussionmentioning

confidence: 99%

Erythropoietin treatment alleviates ultrastructural myelin changes induced by murine cerebral malaria

Hempel

Hyttel

Staalsøe

et al. 2012

Malar J

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“…Histopathological observations and other evidence have established that hemorrhage, sequestration of parasitized red blood cells (PRBC) and leukocytes, and increased blood-brain barrier permeability occur in both human and murine cerebral malaria (Toro and Roman, 1978; Thumwood et al, 1988; Das et al, 1991; Chan-Ling et al, 1992; Patnaik et al, 1994; Turner et al, 1994; Brown et al, 1999a, 2001; White et al, 2001; van der Heyde et al, 2001; Adams et al, 2002; Grau et al, 2003; Hunt and Grau, 2003; Taylor et al, 2004; Amante et al, 2010; Claser et al, 2011; Cunnington et al, 2013). Examples of these phenomena from the experimental model are shown in Figures 1–3.…”

Section: Severe Malariamentioning

confidence: 99%

Cerebral malaria: gamma-interferon redux

Hunt

Ball

Hansen

et al. 2014

Front. Cell. Infect. Microbiol.

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There are two theories that seek to explain the pathogenesis of cerebral malaria, the mechanical obstruction hypothesis and the immunopathology hypothesis. Evidence consistent with both ideas has accumulated from studies of the human disease and experimental models. Thus, some combination of these concepts seems necessary to explain the very complex pattern of changes seen in cerebral malaria. The interactions between malaria parasites, erythrocytes, the cerebral microvascular endothelium, brain parenchymal cells, platelets and microparticles need to be considered. One factor that seems able to knit together much of this complexity is the cytokine interferon-gamma (IFN-γ). In this review we consider findings from the clinical disease, in vitro models and the murine counterpart of human cerebral malaria in order to evaluate the roles played by IFN-γ in the pathogenesis of this often fatal and debilitating condition.

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“…This standard clinical definition misclassifies 25–30% of patients, and can be improved by the addition of retinal examination to identify features specific for histologically defined cerebral malaria (HCM) (Karney and Tong, 1972; Lewallen et al, 1993, 1999, 2000; Beare et al, 2004, 2006; Taylor et al, 2004). The pathogenesis of cerebral malaria remains controversial, and the precise pathway from illness to death difficult to discern; evidence exists to suggest a variety of plausible pathways and a number of individual factors which could impinge upon those pathways (Toro and Roman, 1978; Looareesuwa et al, 1983; Gopinathan et al, 1986; Clark et al, 1987, 2003a,b; Oo et al, 1987; Aikawa, 1988; Pongponratn et al, 1991; Aikawa et al, 1992; Nagatake et al, 1992; Molyneux et al, 1993; Patnaik et al, 1994; Turner et al, 1994; Nakazawa et al, 1995; Lucas et al, 1997; Richards, 1997; Newton et al, 1998; Lou et al, 2001; Piguet et al, 2002; Clark and Cowden, 2003; Liechti et al, 2003; Lopansri et al, 2003; Pino et al, 2003, 2005; Dzeing-Ella et al, 2005; Maguire et al, 2005; Viebig et al, 2005; Wassmer et al, 2005; Kaestli et al, 2006; Montgomery et al, 2006, 2007; Seydel et al, 2006; Dondorp et al, 2008; Milner et al, 2008). Similarly, understanding the causes of mortality, including the etiology and significance of increased brain volume (e.g., cerebral edema vs. other causes), has not been straightforward (Spitz, 1946; MacPherson et al, 1985; Taylor et al, 2004; Milner et al, 2012, 2013a).…”

Section: Introductionmentioning

confidence: 99%

The systemic pathology of cerebral malaria in African children

Milner

Whitten²,

Kamiza

et al. 2014

Front. Cell. Infect. Microbiol.

118

138

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Pediatric cerebral malaria carries a high mortality rate in sub-Saharan Africa. We present our systematic analysis of the descriptive and quantitative histopathology of all organs sampled from a series of 103 autopsies performed between 1996 and 2010 in Blantyre, Malawi on pediatric cerebral malaria patients and control patients (without coma, or without malaria infection) who were clinically well characterized prior to death. We found brain swelling in all cerebral malaria patients and the majority of controls. The histopathology in patients with sequestration of parasites in the brain demonstrated two patterns: (a) the “classic” appearance (i.e., ring hemorrhages, dense sequestration, and extra-erythrocytic pigment) which was associated with evidence of systemic activation of coagulation and (b) the “sequestration only” appearance associated with shorter duration of illness and higher total burden of parasites in all organs including the spleen. Sequestration of parasites was most intense in the gastrointestinal tract in all parasitemic patients (those with cerebral malarial and those without).

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Cerebral Malaria

Cited by 102 publications

References 20 publications

Erythropoietin treatment alleviates ultrastructural myelin changes induced by murine cerebral malaria

Erythropoietin treatment alleviates ultrastructural myelin changes induced by murine cerebral malaria

Cerebral malaria: gamma-interferon redux

The systemic pathology of cerebral malaria in African children

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