Publication: A clinicopathological correlation of the expression of the angiopoietin-Tie-2 receptor pathway in the brain of adults with Plasmodium falciparum malaria
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Issued Date
2013
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eng
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Mahidol University
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BioMed Central
Bibliographic Citation
Malaria Journal. Vol.12, (2013), 50
Suggested Citation
Panote Prapansilp, Isabelle Medana, Nguyen Thi Hoan Mai, Day, Nicholas PJ, Phu, Nguyen Hoan, Yeo, Tsin W, Hien, Tran Tinh, Nicholas J White, Anstey, Nicholas M, Turner, Gareth DH A clinicopathological correlation of the expression of the angiopoietin-Tie-2 receptor pathway in the brain of adults with Plasmodium falciparum malaria. Malaria Journal. Vol.12, (2013), 50. Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/3066
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Title
A clinicopathological correlation of the expression of the angiopoietin-Tie-2 receptor pathway in the brain of adults with Plasmodium falciparum malaria
Abstract
Background: Plasma angiopoietin (Ang)-2 is associated with disease severity and mortality in adults and children
with falciparum malaria. However the mechanism of action of the angiopoietins in fatal malaria is unclear. This
study aimed to determine whether the expression of Ang-1 and Ang-2 and their receptor Tie-2 in cerebral
endothelial or parenchymal cells was specific to cerebral malaria (CM), correlated with coma or other severe clinical
features, and whether plasma and CSF levels of these markers correlated with the clinical and neuropathological
features of severe and fatal malaria in Vietnamese adults.
Methods: Immunohistochemistry was performed for Ang-1, Ang-2 and Tie-2 on post-mortem brain tissue from
fatal malaria cases and controls. Quantitative ELISA for plasma and cerebrospinal fluid levels of Ang-1, Ang-2 and
Tie-2 was done to compare fatal cases with surviving patients from the same study.
Results: Immunohistochemistry revealed significant differences in expression in endothelial and parenchymal cells
compared to controls. However there was no significant difference in expression of these markers on endothelial
cells, astroglial cells or neurons between CM and non-cerebral malaria cases. Immunostaining of Ang-1, Ang-2 and
Tie-2 was also not associated with Plasmodium falciparum-infected erythrocyte sequestration in the brain. However
Ang-1 and Ang-2 expression in neurons was significantly correlated with the incidence of microscopic
haemorrhages. Plasma levels of Ang-2 and Ang-2/Ang-1 ratio were associated with the number of severe malaria
complications and were significant and independent predictors of metabolic acidosis and fatal outcome.
Conclusions: The independent prognostic significance of Ang-2 and the Ang-2/Ang-1 ratio in severe malaria was
confirmed, although immunohistochemistry in fatal cases did not reveal increased expression on brain endothelium
in cerebral versus non-cerebral cases. Activation of the Ang-Tie-2 pathway in severe malaria is therefore related to
acidosis, number of severity criteria and outcome, but is not a specific event in the brain during cerebral malaria.