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

Original Article

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.

Keywords

Aminopropyl carbazole Ischemic stroke Neuroprotection P7C3-A20 Therapeutic window 

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  1. 1.Department of Neurological Surgery, Neuroscience ProgramUniversity of Miami Miller School of MedicineMiamiUSA
  2. 2.The Miami Project to Cure ParalysisUniversity of Miami Miller School of MedicineMiamiUSA
  3. 3.Department of Psychiatry, College of MedicineUniversity of Iowa Carver College of MedicineIowa CityUSA
  4. 4.Department of NeurologyUniversity of Iowa Carver College of MedicineIowa CityUSA
  5. 5.Department of Free Radical and Radiation Biology Program, Department of Radiation Oncology Comprehensive Cancer Center, Department of Veterans AffairsUniversity of Iowa Carver College of MedicineIowa CityUSA
  6. 6.Department of Neurological SurgeryUniversity of Miami, Leonard M. Miller School of MedicineMiamiUSA

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