title: Erythropoietin treatment alleviates ultrastructural myelin changes induced by murine cerebral malaria.
abstract: BACKGROUND
  Cerebral malaria (CM) is a severe complication of malaria with considerable mortality. In addition to acute encephalopathy, survivors frequently suffer from neurological sequelae. The pathogenesis is incompletely understood, hampering the development of an effective, adjunctive therapy, which is not available at present. Previously, erythropoietin (EPO) was reported to significantly improve the survival and outcome in a murine CM model. The study objectives were to assess myelin thickness and ultrastructural morphology in the corpus callosum in murine CM and to adress the effects of EPO treatment in this context.
  
  
  METHODS
  The study consisted of two groups of Plasmodium berghei-infected mice and two groups of uninfected controls that were either treated with EPO or placebo (n = 4 mice/group). In the terminal phase of murine CM the brains were removed and processed for electron microscopy. Myelin sheaths in the corpus callosum were analysed with transmission electron microscopy and stereology.
  
  
  RESULTS
  The infection caused clinical CM, which was counteracted by EPO. The total number of myelinated axons was identical in the four groups and mice with CM did not have reduced mean thickness of the myelin sheaths. Instead, CM mice had significantly increased numbers of abnormal myelin sheaths, whereas EPO-treated mice were indistinguishable from uninfected mice. Furthermore, mice with CM had frequent and severe axonal injury, pseudopodic endothelial cells, perivascular oedemas and intracerebral haemorrhages.
  
  
  CONCLUSIONS
  EPO treatment reduced clinical signs of CM and reduced cerebral pathology. Murine CM does not reduce the general thickness of myelin sheaths in the corpus callosum.
authors: Centre for Medical Parasitology, Department of International Health, Immunology and Microbiology, University of Copenhagen, Copenhagen University Hospital, Denmark. casperhempel@gmail.com
authors: Casper
authors: C
authors: Hempel
authors: Poul
authors: P
authors: Hyttel
authors: Trine
authors: T
authors: Staalsø
authors: Jens R
authors: JR
authors: Nyengaard
authors: Jørgen A L
authors: JA
authors: Kurtzhals
mesh_terms: D000818:Animals; D003337:Corpus Callosum / Q000473:pathology; D004921:Erythropoietin / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D016779:Malaria, Cerebral / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008854:Microscopy, Electron; D009186:Myelin Sheath / Q000473:pathology*; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D010919:Placebos / Q000008:administration & dosage; D010962:Plasmodium berghei / Q000472:pathogenicity; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D010919:Placebos; D004921:Erythropoietin