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http://hdl.handle.net/10261/103294
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dc.contributor.author | Lorrio, Silvia | - |
dc.contributor.author | Gómez-Rangel, Vanessa | - |
dc.contributor.author | Negredo, Pilar | - |
dc.contributor.author | Egea, Javier | - |
dc.contributor.author | León, Rafael | - |
dc.contributor.author | Romero, Alejandro | - |
dc.contributor.author | Dal-Cim, Tharine. | - |
dc.contributor.author | Villarroya, Mercedes | - |
dc.contributor.author | Rodríguez-Franco, María Isabel | - |
dc.contributor.author | Conde, Santiago | - |
dc.contributor.author | Arce, Mariana P. | - |
dc.contributor.author | Roda, José María | - |
dc.contributor.author | García, Antonio G. | - |
dc.contributor.author | López, Manuela G. | - |
dc.date.accessioned | 2014-10-14T08:08:03Z | - |
dc.date.available | 2014-10-14T08:08:03Z | - |
dc.date.issued | 2013 | - |
dc.identifier | doi: 10.1016/j.neuropharm.2012.12.001 | - |
dc.identifier | issn: 0028-3908 | - |
dc.identifier | e-issn: 1873-7064 | - |
dc.identifier.citation | Neuropharmacology 67: 403- 411 (2013) | - |
dc.identifier.uri | http://hdl.handle.net/10261/103294 | - |
dc.description.abstract | ITH33/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.publisher | Elsevier | - |
dc.rights | closedAccess | - |
dc.subject | Free radicals | - |
dc.subject | Photothrombotic stroke | - |
dc.subject | Oxygen and glucose deprivation | - |
dc.subject | ITH33/IQM9.21 | - |
dc.subject | Hippocampal slices | - |
dc.subject | GSH | - |
dc.subject | iNOS | - |
dc.subject | Neuroprotection | - |
dc.title | Novel multitarget ligand ITH33/IQM9.21 provides neuroprotection in in vitro and in vivo models related to brain ischemia | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1016/j.neuropharm.2012.12.001 | - |
dc.date.updated | 2014-10-14T08:08:03Z | - |
dc.description.version | Peer Reviewed | - |
dc.language.rfc3066 | eng | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.openairetype | artículo | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | none | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.fulltext | No Fulltext | - |
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