Pre-clinical models in pediatric traumatic brain injury-challenges and lessons learned. 2017

Patrick M Kochanek, and Jessica S Wallisch, and Hülya Bayır, and Robert S B Clark
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. kochanekpm@ccm.upmc.edu.

OBJECTIVE 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.

UI MeSH Term Description Entries
D007223 Infant A child between 1 and 23 months of age. Infants
D002675 Child, Preschool A child between the ages of 2 and 5. Children, Preschool,Preschool Child,Preschool Children
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000070642 Brain Injuries, Traumatic A form of acquired brain injury which occurs when a sudden trauma causes damage to the brain. Trauma, Brain,Traumatic Brain Injury,Encephalopathy, Traumatic,Injury, Brain, Traumatic,TBI (Traumatic Brain Injury),TBIs (Traumatic Brain Injuries),Traumatic Encephalopathy,Brain Injury, Traumatic,Brain Trauma,Brain Traumas,Encephalopathies, Traumatic,TBI (Traumatic Brain Injuries),Traumas, Brain,Traumatic Brain Injuries,Traumatic Encephalopathies
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D016206 Databases, Bibliographic Extensive collections, reputedly complete, of references and citations to books, articles, publications, etc., generally on a single subject or specialized subject area. Databases can operate through automated files, libraries, or computer disks. The concept should be differentiated from DATABASES, FACTUAL which is used for collections of data and facts apart from bibliographic references to them. Bibliographic Database,Bibliographic Databases,Database, Bibliographic

Related Publications

Patrick M Kochanek, and Jessica S Wallisch, and Hülya Bayır, and Robert S B Clark
January 2017, The Journal of head trauma rehabilitation,
Patrick M Kochanek, and Jessica S Wallisch, and Hülya Bayır, and Robert S B Clark
January 2016, U.S. Army Medical Department journal,
Patrick M Kochanek, and Jessica S Wallisch, and Hülya Bayır, and Robert S B Clark
January 2012, Rehabilitation research and practice,
Patrick M Kochanek, and Jessica S Wallisch, and Hülya Bayır, and Robert S B Clark
May 2024, Journal of neurotrauma,
Patrick M Kochanek, and Jessica S Wallisch, and Hülya Bayır, and Robert S B Clark
January 2006, Developmental neuroscience,
Patrick M Kochanek, and Jessica S Wallisch, and Hülya Bayır, and Robert S B Clark
January 2021, Journal of special operations medicine : a peer reviewed journal for SOF medical professionals,
Patrick M Kochanek, and Jessica S Wallisch, and Hülya Bayır, and Robert S B Clark
January 2016, Methods in molecular biology (Clifton, N.J.),
Patrick M Kochanek, and Jessica S Wallisch, and Hülya Bayır, and Robert S B Clark
January 2016, Methods in molecular biology (Clifton, N.J.),
Patrick M Kochanek, and Jessica S Wallisch, and Hülya Bayır, and Robert S B Clark
November 1996, Journal of learning disabilities,
Patrick M Kochanek, and Jessica S Wallisch, and Hülya Bayır, and Robert S B Clark
January 1997, NeuroRehabilitation,
Copied contents to your clipboard!