dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorAra, Jahan
dc.creatorFekete, Saskia
dc.creatorFrank, Melissa
dc.creatorGolden, Jeffrey A.
dc.creatorPleasure, David
dc.creatorValencia, Ignacio
dc.date2014-05-20T13:38:02Z
dc.date2016-10-25T16:54:26Z
dc.date2014-05-20T13:38:02Z
dc.date2016-10-25T16:54:26Z
dc.date2011-08-01
dc.date.accessioned2017-04-05T20:34:31Z
dc.date.available2017-04-05T20:34:31Z
dc.identifierNeurobiology of Disease. San Diego: Academic Press Inc. Elsevier B.V., v. 43, n. 2, p. 473-485, 2011.
dc.identifier0969-9961
dc.identifierhttp://hdl.handle.net/11449/13193
dc.identifierhttp://acervodigital.unesp.br/handle/11449/13193
dc.identifier10.1016/j.nbd.2011.04.021
dc.identifierWOS:000292069900019
dc.identifierhttp://dx.doi.org/10.1016/j.nbd.2011.04.021
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/860590
dc.descriptionPreconditioning-induced ischemic tolerance has been documented in the newborn brain, however, the signaling mechanisms of this preconditioning require further elucidation. The aims of this study were to develop a hypoxic-preconditioning (PC) model of ischemic tolerance in the newborn piglet, which emulates important clinical similarities to human situation of birth asphyxia, and to characterize some of the molecular mechanisms shown to be implicated in PC-induced neuroprotection in rodent models. One day old piglets were subjected to PC (8% O(2)/92% N(2)) for 3 h and 24 h later were exposed to hypoxia-ischemia (HI) produced by a combination of hypoxia (5% FiO(2)) for a period of 30 min and ischemia induced by a period of hypotension (10 min of reduced mean arterial blood pressure; 70% of baseline). Neuropathologic analysis and unbiased stereology, conducted at 24 h, 3 and 7 days of recovery following HI, indicated a substantial reduction in the severity of brain damage in PC piglets compared to non-PC piglets (P<0.05). PC significantly increased the mRNA expression of hypoxia-inducible factor-1 alpha (HIF-1 alpha) and its target gene, vascular endothelial growth factor (VEGF) at 0 h, 6 h, 24 h, 3 and 7 days of recovery. Immunoblot analysis demonstrated that PC resulted in HIF-1 alpha protein stabilization and accumulation in nuclear extracts of cerebral cortex of newborn piglet brain compared to normoxic controls. Protein levels of VEGF increased in a time-dependent manner in both cortex and hippocampus following PC. Double-immunolabeling indicated that VEGF is mainly expressed in neurons, endothelial cells and astroglia. Our study demonstrates for the first time the protective efficacy of PC against hypoxic-ischemic injury in newborn piglet model, which recapitulates many pathophysiological features of asphyxiated human neonates. Furthermore, as has been shown in rodent models of preconditioning, our results suggest that PC-induced protection in neonatal piglets may involve upregulation of VEGF. (C) 2011 Elsevier B.V. All rights reserved.
dc.languageeng
dc.publisherAcademic Press Inc. Elsevier B.V.
dc.relationNeurobiology of Disease
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectNeuroprotection
dc.subjectHypoxic-preconditioning
dc.subjectPiglet
dc.subjectNewborn brain
dc.subjectHypoxia-ischemia
dc.subjectVEGF
dc.titleHypoxic-preconditioning induces neuroprotection against hypoxia-ischemia in newborn piglet brain
dc.typeOtro


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