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Pre-clinical models in pediatric traumatic brain injury—challenges and lessons learned

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Abstract

Purpose

Despite the enormity of the problem and the lack of new therapies, research in the pre-clinical arena specifically using pediatric traumatic brain injury (TBI) models is limited. In this review, some of the key models addressing both the age spectrum of pediatric TBI and its unique injury mechanisms will be highlighted. Four topics will be addressed, namely, (1) unique facets of the developing brain important to TBI model development, (2) a description of some of the most commonly used pre-clinical models of severe pediatric TBI including work in both rodents and large animals, (3) a description of the pediatric models of mild TBI and repetitive mild TBI that are relatively new, and finally (4) a discussion of challenges, gaps, and potential future directions to further advance work in pediatric TBI models.

Methods

This narrative review on the topic of pediatric TBI models was based on review of PUBMED/Medline along with a synthesis of information on key factors in pre-clinical and clinical developmental brain injury that influence TBI modeling.

Results

In the contemporary literature, six types of models have been used in rats including weight drop, fluid percussion injury (FPI), impact acceleration, controlled cortical impact (CCI), mechanical shaking, and closed head modifications of CCI. In mice, studies are largely restricted to CCI. In large animals, FPI and rotational injury have been used in piglets and shake injury has also been used in lambs. Most of the studies have been in severe injury models, although more recently, studies have begun to explore mild and repetitive mild injuries to study concussion.

Conclusions

Given the emerging importance of TBI in infants and children, the morbidity and mortality that is produced, along with its purported link to the development of chronic neurodegenerative diseases, studies in these models merit greater systematic investigations along with consortium-type approaches and long-term follow-up to translate new therapies to the bedside.

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Acknowledgments

We thank NICHD T32 HD 040686 for the support (JW).

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Authors and Affiliations

  1. Departments of Critical Care Medicine, Anesthesiology, Pediatrics, Bioengineering, and Clinical and Translational Science, Safar Center for Resuscitation Research, Children’s Hospital of Pittsburgh of UPMC, John G. Rangos Research Center, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA

    Patrick M. Kochanek

  2. Safar Center for Resuscitation Research, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Ave, Pittsburgh, PA, 15224, USA

    Jessica S. Wallisch, Hülya Bayır & Robert S. B. Clark

  3. Department of Critical Care Medicine, University of Pittsburgh School of Medicine, 3550 Terrace Street, Scaife Hall, Pittsburgh, PA, 15261, USA

    Jessica S. Wallisch, Hülya Bayır & Robert S. B. Clark

  4. Department of Pediatrics, Children’s Hospital of Pittsburgh of UPMC, University of Pittsburgh School of Medicine, 4401 Penn Avenue, Pittsburgh, PA, 15224, USA

    Hülya Bayır & Robert S. B. Clark

  5. Pittsburgh Center for Free Radical and Antioxidant Health, University of Pittsburgh School of Medicine, 100 Technology Drive, Pittsburgh, PA, 15219, USA

    Hülya Bayır

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  1. Patrick M. Kochanek
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Correspondence to Patrick M. Kochanek.

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Kochanek, P.M., Wallisch, J.S., Bayır, H. et al. Pre-clinical models in pediatric traumatic brain injury—challenges and lessons learned. Childs Nerv Syst 33, 1693–1701 (2017). https://doi.org/10.1007/s00381-017-3474-2

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