Abstract 7

Background. Erythropoietin (Epo) and its receptor have been identified in the human CNS from early fetal life to adulthood, but its function during neurodevelopment or indeed, during normal homeostasis is unknown. Since Epo increases during hypoxemia, we hypothesized that Epo is neuroprotective, at physiologic concentrations. Materials and Methods. To test this, we pretreated human neuronal precursor cells, NT2 cells, for 16 hrs with either 50mU/mL rEpo, 50mU/mL rEpo+neutralizing antiEpo antibody (150 L/mL), or PBS (n=20 each). We have previously documented Epo concentrations in neonatal CSF as high as 68 mU/mL, thus 50 mU/mL is within the physiologic range. Cells were exposed to 14 sec UV irradiation (vs no UV control). After 16 hrs, cells were stained with trypan blue and counted. Nuclear matrix protein released into the media was measured by ELISA, and DNA fragmentation was evaluated by Klenow labelling. Results. Cells exposed to 50 mU/mL Epo were rescued from UV-induced apoptotic cell death, as evaluated by all measures (p 0.0001). Conclusions. We conclude that inhibiting apoptotic cell death might be one function of Epo in the CNS, and we have ongoing studies to determine the mechanism by which this occurs.