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dc.contributor.authorLorrio, Silvia-
dc.contributor.authorGómez-Rangel, Vanessa-
dc.contributor.authorNegredo, Pilar-
dc.contributor.authorEgea, Javier-
dc.contributor.authorLeón, Rafael-
dc.contributor.authorRomero, Alejandro-
dc.contributor.authorDal-Cim, Tharine.-
dc.contributor.authorVillarroya, Mercedes-
dc.contributor.authorRodríguez-Franco, María Isabel-
dc.contributor.authorConde, Santiago-
dc.contributor.authorArce, Mariana P.-
dc.contributor.authorRoda, José María-
dc.contributor.authorGarcía, Antonio G.-
dc.contributor.authorLópez, Manuela G.-
dc.date.accessioned2014-10-14T08:08:03Z-
dc.date.available2014-10-14T08:08:03Z-
dc.date.issued2013-
dc.identifierdoi: 10.1016/j.neuropharm.2012.12.001-
dc.identifierissn: 0028-3908-
dc.identifiere-issn: 1873-7064-
dc.identifier.citationNeuropharmacology 67: 403- 411 (2013)-
dc.identifier.urihttp://hdl.handle.net/10261/103294-
dc.description.abstractITH33/IQM9.21 is a novel compound belonging to a family of glutamic acid derivatives, synthesized under the hypothesis implying that multitarget ligands may provide more efficient neuroprotection than single-targeted compounds. In rat hippocampal slices, oxygen plus glucose deprivation followed by re-oxygenation (OGD/Reox) elicited 42% cell death. At 1 μM, ITH33/IQM9.21 mitigated this damage by 26% and by 55% at 3 μM. OGD/Reox also elicited mitochondrial depolarization, overproduction of reactive oxygen species (ROS), enhanced expression of nitric oxide synthase (iNOS) and reduction of GSH levels. These changes were almost fully prevented when 3 μM ITH33/IQM9.21 was present during slice treatment with OGD/Reox. In isolated hippocampal neurons, ITH33/IQM9.21 reduced [Ca2+]c transients induced by a high K+ depolarizing solution or glutamate. In a photothrombotic model of stroke in mice, intraperitoneal injection of ITH33/IQM9.21 at 1.25 mg/kg, 2.5 mg/kg or 5 mg/kg given before and during 2 days after stroke induction, reduced infarct volume by over 45%. Furthermore, when the compound was administered 1 h post-stroke, a similar effect was observed. In conclusion, these in vitro and in vivo results suggest that ITH33/IQM9.21 exhibits neuroprotective effects to protect the vulnerable neurons at the ischemic penumbra by an effective and multifaceted mechanism, mediated by reduction of Ca2+ overload, providing mitochondrial protection and antioxidant actions.-
dc.publisherElsevier-
dc.rightsclosedAccess-
dc.subjectFree radicals-
dc.subjectPhotothrombotic stroke-
dc.subjectOxygen and glucose deprivation-
dc.subjectITH33/IQM9.21-
dc.subjectHippocampal slices-
dc.subjectGSH-
dc.subjectiNOS-
dc.subjectNeuroprotection-
dc.titleNovel multitarget ligand ITH33/IQM9.21 provides neuroprotection in in vitro and in vivo models related to brain ischemia-
dc.typeartículo-
dc.identifier.doi10.1016/j.neuropharm.2012.12.001-
dc.date.updated2014-10-14T08:08:03Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.openairetypeartículo-
item.cerifentitytypePublications-
item.grantfulltextnone-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.fulltextNo Fulltext-
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