Survival of hippocampal neurons in culture upon hypoxia: effect of erythropoietin

The potential of erythropoietin (EPO) to reduce hypoxia-induced cell death has been investigated in 5-day-old primary cultures of rat postnatal hippoc ampal neurons. Application of EPO (100 pM) at the start of hypoxia resulted in a significant reduction of neuronal death (33.0 +/- 7.5% in cells incub ated with EPO vs 56.75 +/- 7.3% in non-treated cells; n = 4, p < 0.021). Si miliar results were obtained upon application of cycloheximide (CHX; 1 <mu> M) simultaneously with hypoxia (34.75 +/- 5.6% vs 56.75 +/- 7.3% with and w ithout CHX, respectively, n = 4, p < 0.035), indicating that hypoxia-induce d neuronal death is an active, protein synthesis-dependent process. Both, E PO and EPO receptor (EPOR) were found to; be expressed after hypoxia in hip pocampal neurons in vitro and in vivo. These results demonstrate for the fi rst time that EPO can reverse hypoxia-induced neuronal death when applied s imultaneously with the hypoxic stimulus. NeuroReport 11:3485-3488 (C) 2000 Lippincott Williams & Wilkins.