Endothelin in a murine model of cerebral malaria

Fabiana S. Machado, Mahalia S. Desruisseaux, Nagajyothi, Richard P. Kennan, Hoby P. Hetherington, Murray Wittner, Louis M. Weiss, Sunhee C. Lee, Philipp E. Scherer, Moriya Tsuji, Herbert B. Tanowitz

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34 Scopus citations

Abstract

Cerebral malaria (CM) remains a deadly complication of Plasmodium falciparum infection, and children are at high risk of developing encephalopathy as a result of CM. This is probably a consequence of the activation of many of the inflammatory cytokines as well as the glial cells and the vascular endothelium in the brain. We have previously demonstrated that there is a striking reduction in cerebral blood flow by magnetic resonance imaging when mice are infected with Plasmodium berghei ANKA (PbA), and we now demonstrate a possible role for endothelin (ET-1) in the pathogenesis of CM. The brains of female C57BL/6 mice with PbA infection were examined at Day 5 for the expression of ET-1, endothelin converting enzyme (ECE), and the endothelin receptors A and B (ETA and ETB) by both reverse transcription-polymerase chain reaction (RT-PCR) and quantitative real-time PCR. ET-1 and ECE mRNA expression was markedly increased by RT-PCR in PbA-infected mice. Real-time quantitative PCR demonstrated a 3-fold increase in ET-1 (P < 0.05) and a significant increase in ETA and ETB expression (P , 0.05) in PbA-infected mice. Histopathology of PbA-infected mice demonstrated a transformation in the morphology of microglial cells and clustering of these cells consistent with activation. Though the full impact of ET-1 on CM remains to be elucidated, these findings demonstrate that in the murine model, there is a significant increase in ET-1 and its components, which is associated with the vasculopathy and immunopathology of CM.

Original languageEnglish (US)
Pages (from-to)1176-1181
Number of pages6
JournalExperimental Biology and Medicine
Volume231
Issue number6
StatePublished - Jun 1 2006

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Keywords

  • Cerebral blood flow
  • Cerebral malaria
  • Endothelin
  • Magnetic resonance imaging

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Machado, F. S., Desruisseaux, M. S., Nagajyothi, Kennan, R. P., Hetherington, H. P., Wittner, M., Weiss, L. M., Lee, S. C., Scherer, P. E., Tsuji, M., & Tanowitz, H. B. (2006). Endothelin in a murine model of cerebral malaria. Experimental Biology and Medicine, 231(6), 1176-1181.