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Bench to Cribside: the Path for Developing a Neuroprotectant

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Abstract

The consequences of perinatal brain injury include immeasurable anguish for families and substantial ongoing costs for care and support of effected children. Factors associated with perinatal brain injury in the preterm infant include inflammation and infection, and with increasing gestational age, a higher proportion is related to hypoxic–ischemic events, such as stroke and placental abruption. Over the past decade, we have acquired new insights in the mechanisms underpinning injury and many new tools to monitor outcome in perinatal brain injury in our experimental models. By embracing these new technologies, we can expedite the screening of novel therapies. This is critical as despite enormous efforts of the research community, hypothermia is the only viable neurotherapeutic, and this procedure is limited to term birth and postcardiac arrest hypoxic–ischemic events. Importantly, experimental and preliminary data in humans also indicate a considerable therapeutic potential for melatonin against perinatal brain injury. However, even if this suggested potential is proven, the complexity of the human condition means we are likely to need additional neuroprotective and regenerative strategies. Thus, within this review, we will outline what we consider the key stages of preclinical testing and development for a neuroprotectant or regenerative neurotherapy for perinatal brain injury. We will also highlight examples of novel small animal physiological and behavioral testing that gives small animal preclinical models greater clinical relevance. We hope these new tools and an integrated bench to cribside strategic plan will facilitate the fulfillment of our overarching goal, improving the long-term brain health and quality of life for infants suffering perinatal brain injury.

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Acknowledgments

The authors’ research is funded by the Wellcome Trust (program grant No. WT094823MA), Inserm, Université Paris 7, APHP (Contrat Hospitalier de Recherche Translationnelle, to PG), Fondation Leducq, Fondation Grace de Monaco, Fondation Roger de Spoelberch, PremUP, Legs Poix, AFM, and FRM. We are indebted to Sylvia Fortes for performing the Morris water maze tests.

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Each of the authors declares that they have no conflicts of interest.

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Authors and Affiliations

  1. Inserm U676, Hopital Robert Debre, 48 Blvd Serurier, 75019, Paris, France

    Nelina Ramanantsoa, Bobbi Fleiss, Myriam Bouslama, Boris Matrot, Leslie Schwendimann, Charles Cohen-Salmon, Pierre Gressens & Jorge Gallego

  2. Université Paris Diderot, Faculté de Médecine, Paris, France

    Nelina Ramanantsoa, Bobbi Fleiss, Myriam Bouslama, Boris Matrot, Leslie Schwendimann, Charles Cohen-Salmon, Pierre Gressens & Jorge Gallego

  3. Centre for the Developing Brain, Perinatal Imaging and Health Department, Division of Imaging Sciences, King’s College, London, UK

    Bobbi Fleiss & Pierre Gressens

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  1. Nelina Ramanantsoa
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Correspondence to Bobbi Fleiss.

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Nelina Ramanantsoa and Bobbi Fleiss joint first authorship.Pierre Gressens and Jorge Gallego joint last authorship.

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Ramanantsoa, N., Fleiss, B., Bouslama, M. et al. Bench to Cribside: the Path for Developing a Neuroprotectant. Transl. Stroke Res. 4, 258–277 (2013). https://doi.org/10.1007/s12975-012-0233-2

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  • DOI: https://doi.org/10.1007/s12975-012-0233-2

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