Publication: Induction of the vascular endothelial growth factor pathway in the brain of adults with fatal falciparum malaria is a non-specific response to severe disease
Issued Date
2010-08-01
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ISSN
13652559
03090167
03090167
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2-s2.0-77955777236
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Mahidol University
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SCOPUS
Bibliographic Citation
Histopathology. Vol.57, No.2 (2010), 282-294
Suggested Citation
Isabelle M. Medana, Nicholas P J Day, Rachel Roberts, Navakanit Sachanonta, Helen Turley, Emsri Pongponratn, Tran Tinh Hien, Nicholas J. White, Gareth D H Turner Induction of the vascular endothelial growth factor pathway in the brain of adults with fatal falciparum malaria is a non-specific response to severe disease. Histopathology. Vol.57, No.2 (2010), 282-294. doi:10.1111/j.1365-2559.2010.03619.x Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/29583
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Title
Induction of the vascular endothelial growth factor pathway in the brain of adults with fatal falciparum malaria is a non-specific response to severe disease
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Abstract
Aims: Pathological or neuroprotective mechanisms in the brain in severe malaria may arise from microvascular obstruction with malaria-parasitized erythrocytes. This study aimed to investigate the role of hypoxia and induction of the vascular endothelial growth factor (VEGF) pathway in the neuropathophysiology of severe malaria. Methods and results: Immunohistochemistry was performed on post mortem brain tissue sections from 20 cases of severe malaria and examined for the expression of transcriptional regulators of VEGF [hypoxia-inducible factor-1 alpha (HIF-1), HIF-2], DEC-1, VEGF, VEGF receptors 1 and 2, and the activated, phosphorylated VEGF receptor 2 (pKDR). HIFs showed limited protein expression andor translocation to cell nuclei in severe malaria, but DEC-1, which is more stable and regulated by HIF-1, was observed. There was heterogeneous expression of VEGF and its receptors in severe malaria and non-malarial disease controls. pKDR expression on vessels was greater in malaria cases than in controls but did not correlate with parasite sequestration. VEGF uptake by malaria parasites was observed. Conclusions: VEGF and its receptor expression levels in severe malaria reflect a non-specific response to severe systemic disease. Potential manipulation of events at the vasculature by the parasite requires further investigation. © 2010 Blackwell Publishing Limited.