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01-04-2018 | Original Article

Beneficial Effects of Delayed P7C3-A20 Treatment After Transient MCAO in Rats

Authors: Zachary B. Loris, Justin R. Hynton, Andrew A. Pieper, W. Dalton Dietrich

Published in: Translational Stroke Research | Issue 2/2018

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.

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Title: Beneficial Effects of Delayed P7C3-A20 Treatment After Transient MCAO in Rats
Authors: Zachary B. Loris
Justin R. Hynton
Andrew A. Pieper
W. Dalton Dietrich
Publication date: 01-04-2018
Publisher: Springer US
Published in: Translational Stroke Research / Issue 2/2018
Print ISSN: 1868-4483
Electronic ISSN: 1868-601X
DOI: https://doi.org/10.1007/s12975-017-0565-z

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Beneficial Effects of Delayed P7C3-A20 Treatment After Transient MCAO in Rats

Abstract

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Abstract

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