Plasmodium berghei ANKA: erythropoietin activates neural stem cells in an experimental cerebral malaria model.
Cerebral malaria (CM) causes substantial mortality and neurological sequelae in survivors, and no neuroprotective regimens are currently available for this condition. Erythropoietin (EPO) reduces neuropathology and improves survival in murine CM. Using the Plasmodium berghei model of CM, we investigated if EPO's neuroprotective effects include activation of endogenous neural stem cells (NSC). By using immunohistochemical markers of different NSC maturation stages, we show that EPO increased the number of nestin(+) cells in the dentate gyrus and in the sub-ventricular zone of the lateral ventricles, relative to control-treatment. 75% of the EPO-treated CM mice displayed migration as nestin(+) NSC. The NSC showed differentiation towards a neural cell lineage as shown by PSA-NCAM binding and NSC maturation and lineage commitment was significantly affected by exogenous EPO and by CM in the sub ventricular zone. These results indicate a rapid, EPO-dependent activation of NSC during CM pathology.
Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark. a.core1@nuigalway.ie
Andrew
A
Core
Casper
C
Hempel
Jørgen A L
JA
Kurtzhals
Milena
M
Penkowa
D000704:Analysis of Variance; D000818:Animals; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D007150:Immunohistochemistry; D007381:Intermediate Filament Proteins / Q000032:analysis; D016779:Malaria, Cerebral / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000032:analysis; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1 / Q000032:analysis; D058953:Neural Stem Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D016501:Neurites / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010962:Plasmodium berghei; D012794:Sialic Acids / Q000032:analysis; D013047:Specific Pathogen-Free Organisms
D007381:Intermediate Filament Proteins; D009419:Nerve Tissue Proteins; C577485:Nes protein, mouse; D064231:Nestin; D039842:Neural Cell Adhesion Molecule L1; D018696:Neuroprotective Agents; D012794:Sialic Acids; C046643:alpha-internexin; C103469:polysialyl neural cell adhesion molecule; D004921:Erythropoietin