losartan-potassium and Neural-Tube-Defects

Erythropoiesis-stimulating agents (ESA) improve the hemoglobin level of roughly half the patients receiving chemotherapy for solid tumors or for blood diseases. These figures vary highly between studies. On average, 6 of these patients must be treated with ESA to prevent a transfusion for one patient. The impact of ESA prescription on quality of life is difficult to assess in the studies available today. The medicoeconomic analyses are on the whole unfavorable to the prescription of ESA for chemotherapy-induced anemia. This analysis might change if there were a way to select the patients highly likely to respond to ESA. Concern also exists about the potential negative impact of ESA prescription on patient survival when the objective of the prescription is to normalize hemoglobin. International guidelines must be followed to ensure that under treatment hemoglobin is always less than 12 g/dL.

Topics: Anemia; Erythropoietin; Hematologic Neoplasms; Humans; Neural Tube Defects; Practice Guidelines as Topic

Erythropoietin (EPO) is the principal growth factor regulating the production of red blood cells. Recent studies demonstrated that exogenous EPO acts as a neuroprotectant and regulates neurogenesis. Using a genetic approach, we evaluate the roles of endogenous EPO and its classical receptor (EPOR) in mammalian neurogenesis. We demonstrate severe and identical embryonic neurogenesis defects in animals null for either the Epo or EpoR gene, suggesting that the classical EPOR is essential for EPO action during embryonic neurogenesis. Furthermore, by generating conditional EpoR knock-down animals, we demonstrate that brain-specific deletion of EpoR leads to significantly reduced cell proliferation in the subventricular zone and impaired post-stroke neurogenesis. EpoR conditional knockdown leads to a specific deficit in post-stroke neurogenesis through impaired migration of neuroblasts to the peri-infarct cortex. Our results suggest that both EPO and EPOR are essential for early embryonic neural development and that the classical EPOR is important for adult neurogenesis and for migration of regenerating neurons during post-injury recovery.

Topics: Animals; Brain; Cell Division; Cell Lineage; DNA Replication; Erythropoietin; Gene Expression Regulation, Developmental; In Situ Hybridization; Infarction, Middle Cerebral Artery; Integrases; Mesoderm; Mice; Mice, Inbred C57BL; Mice, Knockout; Nerve Tissue Proteins; Neural Crest; Neural Tube Defects; Neuroepithelial Cells; Neurons; Receptors, Erythropoietin; Regeneration; Stem Cells; Viral Proteins