Recombinant human erythropoietin increases survival and reduces neuronal apoptosis in a murine model of cerebral malaria

• Published in: Malaria Journal
• Main Authors: Hempel Casper, Wiese Lothar, Penkowa Milena, Kirkby Nikolai, Kurtzhals Jørgen AL
• Format: Article in Journal/Newspaper
• Language: English
• Published: BMC 2008
• Subjects: Arctic medicine. Tropical medicine; RC955-962; Infectious and parasitic diseases; RC109-216; Arctic
• Online Access: https://doi.org/10.1186/1475-2875-7-3; https://doaj.org/article/5f19b95f9b974ef1ab4798e5e1e12637

Abstract Background Cerebral malaria (CM) is an acute encephalopathy with increased pro-inflammatory cytokines, sequestration of parasitized erythrocytes and localized ischaemia. In children CM induces cognitive impairment in about 10% of the survivors. Erythropoietin (Epo) has – besides of its well known haematopoietic properties – significant anti-inflammatory, antioxidant and anti-apoptotic effects in various brain disorders. The neurobiological responses to exogenously injected Epo during murine CM were examined. Methods Female C57BL/6j mice (4–6 weeks), infected with Plasmodium berghei ANKA, were treated with recombinant human Epo (rhEpo; 50–5000 U/kg/OD, i.p.) at different time points. The effect on survival was measured. Brain pathology was investigated by TUNEL (Terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labelling), as a marker of apoptosis. Gene expression in brain tissue was measured by real time PCR. Results Treatment with rhEpo increased survival in mice with CM in a dose- and time-dependent manner and reduced apoptotic cell death of neurons as well as the expression of pro-inflammatory cytokines in the brain. This neuroprotective effect appeared to be independent of the haematopoietic effect. Conclusion These results and its excellent safety profile in humans makes rhEpo a potential candidate for adjunct treatment of CM.