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Promoting neuroregeneration after perinatal arterial ischemic stroke: neurotrophic factors and mesenchymal stem cells

Pediatric Research volume 83, pages 372384 (2018) | Download Citation

Abstract

Newborns suffering from perinatal arterial ischemic stroke (PAIS) are at risk of neurodevelopmental problems. Current treatment options for PAIS are limited and mainly focus on supportive care, as presentation of PAIS is beyond the time window of current treatment strategies. Therefore, recent focus has shifted to interventions that stimulate regeneration of damaged brain tissue. From animal models, it is known that the brain increases its neurogenic capability after ischemic injury, by promoting neural cell proliferation and differentiation. However, neurogenesis is not maintained at the long term, which consequently impedes full repair leading to adverse consequences later in life. Boosting neuroregeneration of the newborn brain using treatment with neurotrophic factors and/or mesenchymal stem cells (MSCs) may be promising novel therapeutic strategies to improve neurological prospects and quality of life of infants with PAIS. This review focuses on effectiveness of neurotrophic growth factors, including erythropoietin, brain-derived neurotrophic factor, vascular endothelial growth factor, glial-derived neurotrophic factor, and MSC therapy, in both experimental neonatal stroke studies and first clinical trials for neonatal ischemic brain injury.

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Acknowledgements

We are grateful to Nelleke van der Weerd for her extensive literature search.

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Author notes

    • Manon J N L Benders
    •  & Cora H A Nijboer

    The last two authors contributed equally to this work.

Affiliations

  1. Department of Neonatology, Wilhelmina Children’s Hospital, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands

    • Nienke Wagenaar
    • , Linda S de Vries
    • , Floris Groenendaal
    •  & Manon J N L Benders
  2. Laboratory of NeuroImmunology and Developmental Origins of Disease, University Medical Centre Utrecht, Utrecht University, Utrecht, The Netherlands

    • Caroline G M de Theije
    •  & Cora H A Nijboer

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Competing interests

This study was supported by the Netherlands Organisation for Health Research and Development (ZonMW), the Netherlands (TAS Research Grant 11600200). The authors declare no conflict of interest.

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Correspondence to Cora H A Nijboer.

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https://doi.org/10.1038/pr.2017.243