Linked Life Data

16417583

Source:http://linkedlifedata.com/resource/pubmed/id/16417583

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pubmed-article:16417583pubmed:abstractTextThis study was designed to investigate the neuroprotective effect of intrinsic and extrinsic erythropoietin (EPO) against hypoxia/ischemia, and determine the optimal time-window with respect to the EPO-induced neuroprotection. Experiments were conducted using primary mixed neuronal/astrocytic cultures and neuron-rich cultures. Hypoxia (2%) induces hypoxia-inducible factor-1alpha (HIF-1alpha) activity followed by strong EPO expression in mixed cultures and weak expression in neuron-rich cultures as documented by both western blot and RT-PCR. Immunoreactive EPO was strongly detected in astrocytes, whereas EPOR was only detected in neurons. Neurons were significantly damaged in neuron-rich cultures but were distinctly rescued in mixed cultures. Application of recombinant human EPO (rhEPO) (0.1 U/mL) within 6 h before or after hypoxia significantly increased neuronal survival compared with no rhEPO treatment. Application of rhEPO after onset of reoxygenation achieved the maximal neuronal protection against ischemia/reperfusion injury (6 h hypoxia followed 24 h reoxygenation). Our results indicate that HIF-1alpha induces EPO gene released by astrocytes and acts as an essential mediator of neuroprotection, prove the protective role of intrinsic astrocytic-neuronal signaling pathway in hypoxic/ischemic injury and demonstrate an optimal therapeutic time-window of extrinsic rhEPO in ischemia/reperfusion injury in vitro. The results point to the potential beneficial effects of HIF-1alpha and EPO for the possible treatment of stroke.lld:pubmed
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pubmed-article:16417583pubmed:dateRevised2011-11-17lld:pubmed
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pubmed-article:16417583pubmed:articleTitleIntrinsic and extrinsic erythropoietin enhances neuroprotection against ischemia and reperfusion injury in vitro.lld:pubmed
pubmed-article:16417583pubmed:affiliationDepartment of Neurology, Juntendo University of School of Medicine, Bunkyo-ku, Tokyo, Japan.lld:pubmed
pubmed-article:16417583pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:16417583pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed
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