Neuronal damage after moderate hypoxia and erythropoietin.
Both mild hypoxia and exogenous erythropoietin may protect the brain against subsequent severe hypoxia, and the conditioning effect of transient hypoxia is partly mediated by hypoxia-induced endogenous erythropoietin. We now observed in several experimental models that combining transient hypoxia and exogenous erythropoietin may cause neuronal damage. High-dose erythropoietin (40 IU/ml) profoundly impeded synaptic transmission of rat hippocampal slice cultures when used in conjunction with moderate hypoxia (10% O2 for two 8-h periods). Addition of erythropoietin increased viability of cultured rat embryonic cortical neurons at 21% O2 but decreased viability under hypoxic conditions (2% O2) in a dose-dependent fashion. Death of human neuronal precursor cells challenged by oxygen and glucose deprivation was increased by erythropoietin when cells were cultured under hypoxic but not under normoxic conditions. In neonatal rats exposed to moderate hypoxia plus erythropoietin, numbers of degenerating cerebral neurons were increased, as compared to controls or rats subjected to either hypoxia or erythropoietin alone. Thus, erythropoietin may aggravate rather than ameliorate neuronal damage when administered during transient hypoxia.
Weber
Astrid
A
Department of Neonatology, Campus Virchow-Klinikum, Berlin, Germany.
Dzietko
Mark
M
Berns
Monika
M
Felderhoff-Mueser
Ursula
U
Heinemann
Uwe
U
Maier
Rolf F
RF
Obladen
Michael
M
Ikonomidou
Chrissanthi
C
Bührer
Christoph
C
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D020520:Brain Infarction / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D018728:Entorhinal Cortex / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D004921:Erythropoietin / Q000633:toxicity*; D005947:Glucose / Q000172:deficiency; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007231:Infant, Newborn; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009498:Neurotoxins / Q000633:toxicity; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D013234:Stem Cells / Q000187:drug effects / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D009498:Neurotoxins; D004921:Erythropoietin; D005947:Glucose