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Article Dans Une Revue Stroke Année : 2009

Delayed hypoxic postconditioning protects against cerebral ischemia in the mouse.

Résumé

BACKGROUND AND PURPOSE: Inspired from preconditioning studies, ischemic postconditioning, consisting of the application of intermittent interruptions of blood flow shortly after reperfusion, has been described in cardiac ischemia and recently in stroke. It is well known that ischemic tolerance can be achieved in the brain not only by ischemic preconditioning, but also by hypoxic preconditioning. However, the existence of hypoxic postconditioning has never been reported in cerebral ischemia. METHODS: Adult mice subjected to transient middle cerebral artery occlusion underwent chronic intermittent hypoxia starting either 1 or 5 days after ischemia and brain damage was assessed by T2-weighted MRI at 43 days. In addition, we investigated the potential neuroprotective effect of hypoxia applied after oxygen glucose deprivation in primary neuronal cultures. RESULTS: The present study shows for the first time that a late application of hypoxia (5 days) after ischemia reduced delayed thalamic atrophy. Furthermore, hypoxia performed 14 hours after oxygen glucose deprivation induced neuroprotection in primary neuronal cultures. We found that hypoxia-inducible factor-1alpha expression as well as those of its target genes erythropoietin and adrenomedullin is increased by hypoxic postconditioning. Further studies with pharmacological inhibitors or recombinant proteins for erythropoietin and adrenomedullin revealed that these molecules participate in this hypoxia postconditioning-induced neuroprotection. CONCLUSIONS: Altogether, this study demonstrates for the first time the existence of a delayed hypoxic postconditioning in cerebral ischemia and in vitro studies highlight hypoxia-inducible factor-1alpha and its target genes, erythropoietin and adrenomedullin, as potential effectors of postconditioning.

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Neurosciences
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Dates et versions

hal-00863295 , version 1 (18-09-2013)

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Claire Leconte, Emmanuelle Tixier, Thomas Freret, Jérôme Toutain, Romaric Saulnier, et al.. Delayed hypoxic postconditioning protects against cerebral ischemia in the mouse.. Stroke, 2009, 40 (10), pp.3349-55. ⟨10.1161/STROKEAHA.109.557314⟩. ⟨hal-00863295⟩
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