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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-1alpha), HIF-2alpha], DEC-1, VEGF, VEGF receptors 1 and 2, and the activated, phosphorylated VEGF receptor 2 (pKDR). HIFs showed limited protein expression and/or translocation to cell nuclei in severe malaria, but DEC-1, which is more stable and regulated by HIF-1alpha, 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.

Original publication

DOI

10.1111/j.1365-2559.2010.03619.x

Type

Journal article

Journal

Histopathology

Publication Date

08/2010

Volume

57

Pages

282 - 294

Keywords

Adult, Brain, Case-Control Studies, Humans, Immunohistochemistry, Malaria, Cerebral, Malaria, Falciparum, Microvessels, Transcription Factors, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factor Receptor-2