Plasmodium berghei ANKA: erythropoietin activates neural stem cells in an experimental cerebral malaria model

TY - JOUR

T1 - Plasmodium berghei ANKA: erythropoietin activates neural stem cells in an experimental cerebral malaria model

AU - Core, Andrew

AU - Hempel, Casper

AU - Kurtzhals, Jørgen A L

AU - Penkowa, Milena

N1 - Copyright © 2010 Elsevier Inc. All rights reserved.

PY - 2011/2

Y1 - 2011/2

N2 - 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.

AB - 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.

KW - Analysis of Variance

KW - Animals

KW - Disease Models, Animal

KW - Erythropoietin

KW - Female

KW - Immunohistochemistry

KW - Intermediate Filament Proteins

KW - Malaria, Cerebral

KW - Mice

KW - Mice, Inbred C57BL

KW - Nerve Tissue Proteins

KW - Neural Cell Adhesion Molecule L1

KW - Neural Stem Cells

KW - Neurites

KW - Neuroprotective Agents

KW - Plasmodium berghei

KW - Sialic Acids

KW - Specific Pathogen-Free Organisms

U2 - 10.1016/j.exppara.2010.09.010

DO - 10.1016/j.exppara.2010.09.010

M3 - Journal article

C2 - 21044627

SN - 0014-4894

VL - 127

SP - 500

EP - 505

JO - Experimental Parasitology

JF - Experimental Parasitology

IS - 2

ER -