Advertisement

Cerebral Malaria: Protection by Erythropoietin

  • Anne-Lise Bienvenu
  • Stephane Picot
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 982)

Abstract

Cerebral malaria (CM) is still responsible for unacceptable death rate, while new antimalarial drugs were recently developed. CM pathophysiology shares essential biological features with cerebral ischemia. Because erythropoietin (Epo) was demonstrated to reduce mortality rate during experimental cerebral ischemia (1), in the early 2000, we wondered whether Epo could help to reduce the burden of CM. There is now evidence that Epo high doses could prevent early mortality during cerebral malaria. This evidence was obtained first using mice model of cerebral malaria, and later confirmed by prospective clinical trial in endemic area. High doses of Epo are needed to cross the blood–brain barrier (see Note 1) and to favor the cytoprotective versus hematopoietic effect of this pleiotropic cytokine (see Note 2).

Key words

Erythropoietin Cerebral malaria Neuronal apoptosis Endothelial apoptosis Murine model Neuroprotection CEPO Epo-biosimilars 

References

  1. 1.
    Sakanaka M, Wen TC, Matsuda S et al (1998) In vivo evidence that erythropoietin protects neurons from ischemic damage. Proc Natl Acad Sci U S A 95:4635–4640PubMedCrossRefGoogle Scholar
  2. 2.
    World Health Organization (2010) Guidelines for the treatment of malaria. Second edition, Rev 1PubMedCrossRefGoogle Scholar
  3. 3.
    Newton CR, Krishna S (1998) Severe falciparum malaria in children: current understanding of pathophysiology and supportive treatment. Pharmacol Ther 79:1–53PubMedCrossRefGoogle Scholar
  4. 4.
    Di Perri G, Di Perri IG, Monteiro GB et al (1995) Pentoxifylline as a supportive agent in the treatment of cerebral malaria in children. J Infect Dis 171:1317–1322PubMedCrossRefGoogle Scholar
  5. 5.
    van Hensbroek MB, Palmer A, Onyiorah E et al (1996) The effect of a monoclonal antibody to tumor necrosis factor on survival from childhood cerebral malaria. J Infect Dis 174:1091–1097PubMedCrossRefGoogle Scholar
  6. 6.
    Thuma PE, Mabeza GF, Biemba G et al (1998) Effect of iron chelation therapy on mortality in Zambian children with cerebral malaria. Trans R Soc Trop Med Hyg 92:214–218PubMedCrossRefGoogle Scholar
  7. 7.
    Maiese K, Li F, Chong ZZ (2005) New avenues of exploration for erythropoietin. JAMA 293:90–95PubMedCrossRefGoogle Scholar
  8. 8.
    Bienvenu AL, Ferrandiz J, Kaiser K et al (2008) Artesunate-erythropoietin combination for murine cerebral malaria treatment. Acta Trop 106:104–108PubMedCrossRefGoogle Scholar
  9. 9.
    Juul SE, McPherson RJ, Farrell FX et al (2004) Erythropoietin concentrations in cerebrospinal fluid of nonhuman primates and fetal sheep following high-dose recombinant erythropoietin. Biol Neonate 85:138–144PubMedCrossRefGoogle Scholar
  10. 10.
    Statler PA, McPherson RJ, Bauer LA et al (2007) Pharmacokinetics of high-dose recombinant erythropoietin in plasma and brain of neonatal rats. Pediatr Res 61:671–675PubMedCrossRefGoogle Scholar
  11. 11.
    Brines M, Cerami A (2008) Erythropoietin-mediated tissue protection: reducing collateral damage from the primary injury response. J Intern Med 264:405–432PubMedCrossRefGoogle Scholar
  12. 12.
    Grau GE, Del Giudice G, Lambert PH (1987) Host immune response and pathological expression in malaria: possible implications for malaria vaccines. Parasitology 94:S123–S137PubMedCrossRefGoogle Scholar
  13. 13.
    Clark IA (1987) Cell-mediated immunity in protection and pathology of malaria. Parasitol Today 3:300–305PubMedCrossRefGoogle Scholar
  14. 14.
    Thumwood CM, Hunt NH, Clark IA et al (1988) Breakdown of the blood–brain barrier in murine cerebral malaria. Parasitology 96:579–589PubMedCrossRefGoogle Scholar
  15. 15.
    Taylor TE, Fu WJ, Carr RA et al (2004) Differentiating the pathologies of cerebral malaria by postmortem parasite counts. Nat Med 10:143–145PubMedCrossRefGoogle Scholar
  16. 16.
    Grau GE, Mackenzie CD, Carr RA et al (2003) Platelet accumulation in brain microvessels in fatal pediatric cerebral malaria. J Infect Dis 187:461–466PubMedCrossRefGoogle Scholar
  17. 17.
    de Souza JB, Riley EM (2002) Cerebral malaria: the contribution of studies in animal models to our understanding of immunopathogenesis. Microbes Infect 4:291–300PubMedCrossRefGoogle Scholar
  18. 18.
    Landau I, Boulard Y (1978) Life cycles and morphology. In: Killick-Kendrick R, Peters W (eds) Rodent malaria. Academic, London, pp 53–84Google Scholar
  19. 19.
    Vincke IH, Lips MAH (1948) Un nouveau Plasmodium d’un rongeur sauvage du Congo Plasmodium berghei n. sp. Ann Soc Belg Med Trop 28:97–104Google Scholar
  20. 20.
    Amani V, Boubou MI, Pied S et al (1998) Cloned lines of Plasmodium berghei ANKA differ in their abilities to induce experimental cerebral malaria. Infect Immun 66:4093–4099PubMedGoogle Scholar
  21. 21.
    Polder T, Jerusalem C, Eling W (1983) Topographical distribution of the cerebral lesions in mice infected with Plasmodium berghei. Tropenmed Parasitol 34:235–243PubMedGoogle Scholar
  22. 22.
    Ball HJ, MacDougall HG, McGregor IS et al (2004) Cyclooxygenase-2 in the pathogenesis of murine cerebral malaria. J Infect Dis 189:751–758PubMedCrossRefGoogle Scholar
  23. 23.
    Yoeli M, Hargreaves BJ (1974) Brain capillary blockage produced by a virulent strain of rodent malaria. Science 184:572–573PubMedCrossRefGoogle Scholar
  24. 24.
    Hearn J, Rayment N, Landon DN et al (2000) Immunopathology of cerebral malaria: morphological evidence of parasite sequestration in murine brain microvasculature. Infect Immun 68:5364–5376PubMedCrossRefGoogle Scholar
  25. 25.
    Storring PL, Tiplady RJ, Gaines Das RE et al (1998) Epoetin alfa and beta differ in their erythropoietin isoform compositions and biological properties. Br J Haematol 100:79–89PubMedCrossRefGoogle Scholar
  26. 26.
    Brines M, Patel NS, Villa P et al (2008) Nonerythropoietic, tissue-protective peptides derived from the tertiary structure of erythropoietin. Proc Natl Acad Sci U S A 105:10925–10930PubMedCrossRefGoogle Scholar
  27. 27.
    Leist M, Ghezzi P, Grasso G et al (2004) Derivatives of erythropoietin that are tissue protective but not erythropoietic. Science 305:239–242PubMedCrossRefGoogle Scholar
  28. 28.
    Wang X, Zhu C, Wang X et al (2004) The nonerythropoietic asialoerythropoietin protects against neonatal hypoxia-ischemia as potently as erythropoietin. J Neurochem 91:900–910PubMedCrossRefGoogle Scholar
  29. 29.
    Mun KC, Golper TA (2000) Impaired biological activity of erythropoietin by cyanate carbamylation. Blood Purif 18:13–17PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2013

Authors and Affiliations

  • Anne-Lise Bienvenu
    • 1
  • Stephane Picot
    • 1
  1. 1.Malaria Research Unit, SMITH ICBMS UMR CNRS, UCBL, INSA LyonLyonFrance

Personalised recommendations