Isabelle M. MedanaNicholas P J DayRachel RobertsNavakanit SachanontaHelen TurleyEmsri PongponratnTran Tinh HienNicholas J. WhiteGareth D H TurnerJohn Radcliffe HospitalChurchill HospitalMahidol UniversityCho Quan Hospital2018-09-242018-09-242010-08-01Histopathology. Vol.57, No.2 (2010), 282-29413652559030901672-s2.0-77955777236https://repository.li.mahidol.ac.th/handle/20.500.14594/29583Aims: 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.Mahidol UniversityMedicineArticleSCOPUS10.1111/j.1365-2559.2010.03619.x