Erythropoietin protects primary cultures of rat cortical neurons from hypoxia-induced toxicity through attenuating both glutamate release and NMDA receptor evoked neurotoxicity pathway.
OBJECTIVE
To investigate the neuroprotective effect of EPO against hypoxia, and determine the mechanism with respect to the EPO-induced neuroprotection.


METHODS
Experiments were conducted using primary neuron cultures. Neuron survival and glutamate release were measured after bein insulted by hypoxia. Glutamate concentrations were determined by an HPLC-ECD system.


RESULTS
Neurons were significantly damaged in hypoxia. Application of recombinant human EPO (10(-11) M) within 24 h before hypoxia significantly increased neuronal survival compared with no EPO treatment. Moreover, the enhancing of glutamate release stimulated by hypoxia was inhibited by pretreatment with EPO at a concentration of 10(-11) M. Further studies demonstrated that EPO also prevented glutamate and NMDA insulted neurotoxicity.


CONCLUSIONS
These findings suggest that EPO prevents neuronal death in the cultured cortical neuron, possibly through attenuating both glutamate release and NMDA receptor evoked neurotoxicity pathway.
Department of Pharmacy, Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Xiang
X
Xu
Haibin
H
Dai
Yulan
Y
Shi
D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology* / Q000187:drug effects; D004921:Erythropoietin / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism* / Q000633:toxicity; D006801:Humans; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000187:drug effects
D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D011994:Recombinant Proteins; D004921:Erythropoietin; D018698:Glutamic Acid