Abstract:
:Despite ischemic stroke being the fifth leading cause of death in the USA, there are few therapeutic options available. We recently showed that the neuroprotective compound P7C3-A20 reduced brain atrophy, increased neurogenesis, and improved functional recovery when treatment was initiated immediately post-reperfusion after a 90-min middle cerebral artery occlusion (MCAO). In the present study, we investigated a more clinically relevant therapeutic window for P7C3-A20 treatment after ischemic stroke. MCAO rats were administered P7C3-A20 for 1 week, beginning immediately or at a delayed point, 6 h post-reperfusion. Delayed P7C3-A20 treatment significantly improved stroke-induced sensorimotor deficits in motor coordination and symmetry, as well as cognitive deficits in hippocampal-dependent spatial learning, memory retention, and working memory. In the cerebral cortex, delayed P7C3-A20 treatment significantly increased tissue sparing 7 weeks after stroke and reduced hemispheric infarct volumes 48 h after reperfusion. Despite no reduction in striatal infarct volumes acutely, there was a significant increase in spared tissue volume chronically. In the hippocampus, only immediately treated P7C3-A20 animals had a significant increase in tissue sparing compared to vehicle-treated stroke animals. This structural protection translated into minimal hippocampal-dependent behavioral improvements with delayed P7C3-A20 treatment. However, all rats treated with delayed P7C3-A20 demonstrated a significant improvement in both sensorimotor tasks compared to vehicle controls, suggesting a somatosensory-driven recovery. These results demonstrate that P7C3-A20 improves chronic functional and histopathological outcomes after ischemic stroke with an extended therapeutic window.
journal_name
Transl Stroke Resjournal_title
Translational stroke researchauthors
Loris ZB,Hynton JR,Pieper AA,Dietrich WDdoi
10.1007/s12975-017-0565-zsubject
Has Abstractpub_date
2018-04-01 00:00:00pages
146-156issue
2eissn
1868-4483issn
1868-601Xpii
10.1007/s12975-017-0565-zjournal_volume
9pub_type
杂志文章abstract::The presence of active developmental angiogenesis and vascular outgrowth in the postnatal brain may differentially affect vascular responses to stroke in newborns and adults, but very little is known about the dynamics of vascular injury and re-growth after stroke during the neonatal period. In this study we used a cl...
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journal_title:Translational stroke research
pub_type: 杂志文章,评审
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journal_title:Translational stroke research
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doi:10.1007/s12975-017-0554-2
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journal_title:Translational stroke research
pub_type: 杂志文章,已发布勘误
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journal_title:Translational stroke research
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journal_title:Translational stroke research
pub_type: 杂志文章
doi:10.1007/s12975-017-0591-x
更新日期:2018-08-01 00:00:00
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journal_title:Translational stroke research
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pub_type: 杂志文章
doi:10.1007/s12975-010-0064-y
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doi:10.1007/s12975-014-0358-6
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journal_title:Translational stroke research
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:Translational stroke research
pub_type: 杂志文章
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pub_type: 杂志文章
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更新日期:2011-12-01 00:00:00
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journal_title:Translational stroke research
pub_type: 杂志文章
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journal_title:Translational stroke research
pub_type: 杂志文章
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更新日期:2014-10-01 00:00:00
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journal_title:Translational stroke research
pub_type: 已发布勘误
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更新日期:2020-10-22 00:00:00