Neuroprotection following repeated hypoxia preconditioning (RHP): pivotal role of brain-derived erythropoietin
Résumé
Hypoxic preconditioning is a process by which prior treatment of a sublethal dose of hypoxia renders cells tolerant to otherwise lethal hypoxia insult. In the brain, one of the key mediators of this neuroprotective effect is the brain-derived erythropoietin (EPO). Neuroprotection can be mimicked by systemic administration of elevated dose of recombinant EPO (rEPO), which unfortunately presents adverse effects when used frequently on the long-term in patients at risk to cerebral insults because of its peripheral hypertensive and pro-thrombic effects. Therefore, to moderate the use of rEPO, long-lasting physiological elevation of EPO expression within vulnerable brain areas is proposed as a promising approach to reinforce neuronal robustness. The objectives of this project are to define within a model of repeated hypoxia preconditioning the fundamentals mechanisms underlying neuroprotective effects of brain-derived EPO.
Domaines
Autre [q-bio.OT]
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