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Low Oxygen Post Conditioning as an Efficient Non-pharmacological Strategy to Promote Motor Function After Stroke

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Abstract

Low oxygen post conditioning (LOPC) has shown promising results in terms of neuroprotection after stroke, but the effects on motor function have not been considered. Cortical stroke targeting the motor and sensory cortex was induced by photothrombotic occlusion and after 48 h allocated to LOPC (11% O2) for 2 weeks. Motor impairment was assessed using the cylinder and grid walk tests during the exposure period and for two further weeks upon completion of the intervention. Neuroprotection was evaluated by histological and molecular analysis at two time points. Two weeks of LOPC was sufficient to significantly reduce motor deficits and tissue loss after stroke. This functional improvement was associated with increased capillary density, enhanced levels of BDNF, decreased neuronal loss and decreased microglia activation. These improvements, in most instances, were maintained up to 2 weeks after the end of the treatment. To our knowledge, this is the first study to demonstrate that LOPC induces a persistent improvement in motor function and neuroprotection after stroke, and in doing so provides evidence to support a case for considering taking LOPC forward to early stage clinical research.

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Funding

This study was supported by the Hunter Medical Research Institute, Faculty of Health and Medicine Pilot Grant and The University of Newcastle, Australia.

Author information

Authors and Affiliations

  1. School of Biomedical Sciences and Pharmacy and Priority Research Centre for Stroke and Brain Injury, University of Newcastle, Callaghan, 2308, NSW, Australia

    Giovanni Pietrogrande, Katarzyna Zalewska, Zidan Zhao & Frederick R. Walker

  2. Hunter Medical Research Institute, New Lambton Heights, 2305, NSW, Australia

    Giovanni Pietrogrande, Katarzyna Zalewska, Zidan Zhao, Michael Nilsson & Frederick R. Walker

  3. School of Electrical Engineering and Computing, University of Newcastle, Callaghan, 2308, NSW, Australia

    Sarah J. Johnson

  4. Priority Research Centre for Stroke and Brain Injury, University of Newcastle, Callaghan, 2308, NSW, Australia

    Michael Nilsson

  5. NHMRC Centre of Research Excellence Stroke Rehabilitation and Brain Recovery, Heidelberg, VIC, Australia

    Michael Nilsson & Frederick R. Walker

Authors
  1. Giovanni Pietrogrande
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  2. Katarzyna Zalewska
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  3. Zidan Zhao
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  4. Sarah J. Johnson
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  5. Michael Nilsson
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  6. Frederick R. Walker
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Contributions

Experiments were designed by GP, MN and FRW and performed by GP, KZ and ZZ. Manuscript was written by GP and FRW and edited by GP, SJ, MN and FRW.

Corresponding author

Correspondence to Frederick R. Walker.

Ethics declarations

All experiments were conducted in accordance with the New South Wales Animals Research Act (1985) and the Australian Code of Practice for the use of animals for scientific purposes.

Conflict of Interest

The authors declare that they have no conflicts of interest.

Ethical Approval

All experiments were approved by the University of Newcastle Animal Care and Ethics Committee.

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Pietrogrande, G., Zalewska, K., Zhao, Z. et al. Low Oxygen Post Conditioning as an Efficient Non-pharmacological Strategy to Promote Motor Function After Stroke. Transl. Stroke Res. 10, 402–412 (2019). https://doi.org/10.1007/s12975-018-0656-5

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  • DOI: https://doi.org/10.1007/s12975-018-0656-5

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