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Author Notes:

Correspondence: lwei7@emory.edu

Authors' contributions: MC performed most experiments, data analysis and wrote the first draft of the paper. She also participated in revision of the manuscript.

TCD helped in the experimental design and initiation of the project.

XG performed ischemic surgery in mice, YSK participated in cell culture and animal experiments including behavioral tests.

YX helped with concept development and data analysis, SPY contributed to data analysis, wrote and revised the manuscript, LW developed the concept, in charge of experimental design and data analysis. She provided financial support to this project.

All authors read and approved the final manuscript.

Acknowledgements: We appreciate the comments and final editing of this manuscript by Myles R. McCrary.

Availability of data and materials: The datasets used and/or analyzed during the current study are available from the corresponding author on request.

Consent for publication: No unpublished data from other groups or personal communication is used in this paper.

Ethics approval and consent to participate: This investigation does not involve human subject. All animal experiments and surgical procedures were approved by the Emory University Animal Research Committee (2001290-021015BN) and met NIH standards.

Competing interests: The authors declare that they have no competing interests.

Subjects:

Research Funding:

This study was supported by NIH grants NS075378 (SPY), NS085568 (LW/SPY), NS091585 (LW), AHA Established Investigator Award (LW) and AHA Predoctoral Fellowship Award (MC).

This work was also supported by the NIH grant C06 RR015455 from the Extramural Research Facilities Program of the National Center for Research Resources.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • Ischemic stroke
  • BMSC
  • Intranasal
  • Hypoxic preconditioning
  • Trophic factors
  • MESENCHYMAL STEM-CELLS
  • HYPOXIA-INDUCIBLE FACTOR-1-ALPHA
  • CEREBRAL-ISCHEMIA
  • THERAPEUTIC BENEFITS
  • BRAIN-INJURY
  • INFARCTED HEART
  • FOCAL ISCHEMIA
  • SDF-1 CXCL12
  • ADULT BRAIN
  • TRANSPLANTATION

Delayed and repeated intranasal delivery of bone marrow stromal cells increases regeneration and functional recovery after ischemic stroke in mice

Tools:

Journal Title:

BMC Neuroscience

Volume:

Volume 19

Publisher:

, Pages 20-20

Type of Work:

Article | Final Publisher PDF

Abstract:

Background: Stroke is a leading cause of death and disability worldwide, yet there are limited treatments available. Intranasal administration is a novel non-invasive strategy to deliver cell therapy into the brain. Cells delivered via the intranasal route can migrate from the nasal mucosa to the ischemic infarct and show acute neuroprotection as well as functional benefits. However, there is little information about the regenerative effects of this transplantation method in the delayed phase of stroke. We hypothesized that repeated intranasal deliveries of bone marrow stromal cells (BMSCs) would be feasible and could enhance delayed neurovascular repair and functional recovery after ischemic stroke. Results: Reverse transcription polymerase chain reaction and immunocytochemistry were performed to analyze the expression of regenerative factors including SDF-1α, CXCR4, VEGF and FAK in BMSCs. Ischemic stroke targeting the somatosensory cortex was induced in adult C57BL/6 mice by permanently occluding the right middle cerebral artery and temporarily occluding both common carotid arteries. Hypoxic preconditioned (HP) BMSCs (HP-BMSCs) with increased expression of surviving factors HIF-1α and Bcl-xl (1×10 6 cells/100 μl per mouse) or cell media were administered intranasally at 3, 4, 5, and 6 days after stroke. Mice received daily BrdU (50 mg/kg) injections until sacrifice. BMSCs were prelabeled with Hoechst 33342 and detected within the peri-infarct area 6 and 24 h after transplantation. In immunohistochemical staining, significant increases in NeuN/BrdU and Glut-1/BrdU double positive cells were seen in stroke mice received HP-BMSCs compared to those received regular BMSCs. HP-BMSC transplantation significantly increased local cerebral blood flow and improved performance in the adhesive removal test. Conclusions: This study suggests that delayed and repeated intranasal deliveries of HP-treated BMSCs is an effective treatment to encourage regeneration after stroke.

Copyright information:

© 2018 The Author(s).

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
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