Breakdown of the blood-brain barrier in murine cerebral malaria

Thumwood, Cassandra M.; Hunt, Nicholas H.; Clark, Ian A.; Cowden, W. B.

doi:10.1017/s0031182000080203

Cited by 125 publications

(131 citation statements)

References 26 publications

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“…Changes to the integrity of the BBB may occur through the actions of chemokines, which can cause alterations in tight junction proteins in endothelial cell cultures, with a loss of occludin, claudin-5, zonula occulens-1, and zonula occulens-2 staining (60,61) leading to an increase in BBB permeability to protein, which is a feature of human and murine CM (10,38,62,63). The expression of CCR2 and CCR5 mRNA in the vessels during FMCM (Table III) suggests that endothelial cells could be responsive to chemokines, which might affect the permeability of the BBB.…”

Section: Discussionmentioning

confidence: 99%

Chemokine Gene Expression during Fatal Murine Cerebral Malaria and Protection Due to CXCR3 Deficiency

Miu

Mitchell

Müller

et al. 2008

The Journal of Immunology

139

170

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Cerebral malaria (CM) can be a fatal manifestation of Plasmodium falciparum infection. Using murine models of malaria, we found much greater up-regulation of a number of chemokine mRNAs, including those for CXCR3 and its ligands, in the brain during fatal murine CM (FMCM) than in a model of non-CM. Expression of CXCL9 and CXCL10 RNA was localized predominantly to the cerebral microvessels and in adjacent glial cells, while expression of CCL5 was restricted mainly to infiltrating lymphocytes. The majority of mice deficient in CXCR3 were found to be protected from FMCM, and this protection was associated with a reduction in the number of CD8+ T cells in brain vessels as well as reduced expression of perforin and FasL mRNA. Adoptive transfer of CD8+ cells from C57BL/6 mice with FMCM abrogated this protection in CXCR3−/− mice. Moreover, there were decreased mRNA levels for the proinflammatory cytokines IFN-γ and lymphotoxin-α in the brains of mice protected from FMCM. These data suggest a role for CXCR3 in the pathogenesis of FMCM through the recruitment and activation of pathogenic CD8+ T cells.

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Section: Discussionmentioning

confidence: 99%

Chemokine Gene Expression during Fatal Murine Cerebral Malaria and Protection Due to CXCR3 Deficiency

Miu

Mitchell

Müller

et al. 2008

The Journal of Immunology

139

170

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“…The modi®ed erythrocytes acquire ability to adhere to the BMEC and uninfected erythrocytes (Dobbie et al, 1999;Ockenhouse et al, 1992b), which has been postulated to contribute to the pathogenesis of cerebral malaria (Aikawa, 1988;Miller et al, 1994). Plasmodium-infected erythrocytes adhering to the BMEC lead to increased permeability, progressive deterioration and breakdown of the BBB (Hermsen et al, 1998;Polder et al, 1992;Thumwood et al, 1988).…”

Section: Strategies Of Cns Invasion By Fungi and Parasitesmentioning

confidence: 99%

Molecular and cellular mechanisms for microbial entry into the CNS

Zhang¹,

Tuomanen²

1999

J Neurovirol

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A number of pathogenic microbes including neuroinvasive viruses, bacteria and parasites are capable of entry into the central nervous system (CNS) and cause a variety of clinical manifestations. The cellular and molecular mechanisms for the CNS invasion have been extensively studied in the last two decades. Viruses invade neurons and thereby cause encephalitis or peripheral neuritis, while bacteria enter the cerebrospinal¯uid (CSF) and cause meningitis. In contrast, the mechanisms for parasitic neuroinvasion are much more complex and less clear. The capabilities that enable these elite subsets of pathogens to engineer uptake into the CNS will be the subject of this review.

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“…Protein leakage is detectable using Evans blue dye or radioactive tracers, 3 and occurs very early in the course of infection. 4 This is due to major ultrastructural disruption of endothelial cells, as shown by electron microscopy.…”

Section: Introductionmentioning

confidence: 99%

Blood-brain barrier function in cerebral malaria in Malawian children.

Brown¹,

Rogerson²,

Taylor³

et al. 2001

The American Journal of Tropical Medicine and Hygiene

146

111

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Abstract. Cerebral malaria (CM) is a serious complication of Plasmodium falciparum infection. Binding of parasitized erythrocytes to cerebral endothelium plays a key role in disease pathogenesis. Central nervous system signs and symptoms (coma, seizures, raised intracranial pressure) predominate in African children, whereas in adults, multiorgan system failure is more common. In this study we investigated whether changes in blood-brain barrier (BBB) structure and function are compatible with the signs and symptoms observed in Malawian children with CM. Immunohistochemistry on autopsy brain tissues from eight cases of CM showed activation of endothelial cells and macrophages, and disruption of endothelial intercellular junctions in vessels containing sequestered parasitized erythrocytes, but no gross leakage of plasma proteins. Examination of the partition of albumin between circulating plasma and the cerebrospinal fluid from 72 cases of CM showed subtle but measurable changes compatible with impaired BBB function in malaria. These findings suggest that BBB breakdown occurs in areas of parasite sequestration in CM in African children.

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Breakdown of the blood-brain barrier in murine cerebral malaria

Cited by 125 publications

References 26 publications

Chemokine Gene Expression during Fatal Murine Cerebral Malaria and Protection Due to CXCR3 Deficiency

Chemokine Gene Expression during Fatal Murine Cerebral Malaria and Protection Due to CXCR3 Deficiency

Molecular and cellular mechanisms for microbial entry into the CNS

Blood-brain barrier function in cerebral malaria in Malawian children.

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