Head injury is a leading cause of death and acquired disability in childhood. However, the biomechanics of pediatric head injury are poorly understood, primarily due to, the paucity of age-specific data regarding mechanical properties of immature tissue and its response to specific loads. The interdisciplinary proposed research plan is designed to answer the following question: What mechanisms cause what injuries in children of what age? The long-term objectives of the proposed research plan are to determine mechanical properties of the skull and brain, the loads they can withstand safely, and unique mechanisms for primary brain injury in infants (less than 3 months) and young children (1-3 years). In so doing, the long term impact of proposed research plan will be to open pathways for enhanced traumatic head injury prevention, detection, and treatment strategies specific to infants and toddlers. Both contact and non-contact mechanisms of brain injury will be investigated. The research plan uses an integrated bioengineering approach consisting of animal experiments, human and animal tissue tests, clinical studies, and anthropomorphic surrogates, all complemented by mathematical models to: A) measure pediatric tissue injury thresholds for acute neural, vascular, and blood-brain barrier damage B) measure pediatric skull and brain tissue mechanical properties C) create computational models for infant and toddler head injury using (A) and (B) D) qualitatively validate the computational model predictions with witnessed accidental head injuries in children E) measure loads experienced anthropomorphic surrogates during falls, shakes, and inflicted impacts F) determine the relative roles of impact forces and inertial loads in the etiology of primary brain injuries G) compare the computational simulations with acute clinical data to infer potential mechanisms of injury in non-accidental head injury. The overall hypotheses of the proposed research program are that 1) thresholds for skull fracture and tissue injury and mechanical properties of the brain and skull vary with age, such that both contribute to differences in primary head injuries between infants and toddlers, and 2) the increased compliance of the infant skull results in greater brain tissue injury from impact trauma; and 3) a valid computational model can be created to predict specific primary injuries resulting from a given reported mechanism.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS039679-01A2
Application #
6325038
Study Section
Special Emphasis Panel (ZRG1-MDCN-2 (03))
Program Officer
Michel, Mary E
Project Start
2001-05-15
Project End
2006-04-30
Budget Start
2001-05-15
Budget End
2002-04-30
Support Year
1
Fiscal Year
2001
Total Cost
$561,455
Indirect Cost
Name
University of Pennsylvania
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Atlan, Lorre S; Smith, Colin; Margulies, Susan S (2018) Improved prediction of direction-dependent, acute axonal injury in piglets. J Neurosci Res 96:536-544
Pasquesi, Stephanie A; Margulies, Susan S (2017) Failure and Fatigue Properties of Immature Human and Porcine Parasagittal Bridging Veins. Ann Biomed Eng 45:1877-1889
Ferguson, Michael A; Sutton, Robert M; Karlsson, Michael et al. (2016) Increased platelet mitochondrial respiration after cardiac arrest and resuscitation as a potential peripheral biosignature of cerebral bioenergetic dysfunction. J Bioenerg Biomembr 48:269-79
Maltese, Matthew R; Margulies, Susan S (2016) Biofidelic white matter heterogeneity decreases computational model predictions of white matter strains during rapid head rotations. Comput Methods Biomech Biomed Engin 19:1618-29
Olson, Emily; Badder, Carlie; Sullivan, Sarah et al. (2016) Alterations in Daytime and Nighttime Activity in Piglets after Focal and Diffuse Brain Injury. J Neurotrauma 33:734-40
Sullivan, Sarah; Eucker, Stephanie A; Gabrieli, David et al. (2015) White matter tract-oriented deformation predicts traumatic axonal brain injury and reveals rotational direction-specific vulnerabilities. Biomech Model Mechanobiol 14:877-96
Friess, Stuart H; Bruins, Benjamin; Kilbaugh, Todd J et al. (2015) Differing effects when using phenylephrine and norepinephrine to augment cerebral blood flow after traumatic brain injury in the immature brain. J Neurotrauma 32:237-43
Sullivan, Sarah; Coats, Brittany; Margulies, Susan S (2015) Biofidelic neck influences head kinematics of parietal and occipital impacts following short falls in infants. Accid Anal Prev 82:143-53
Jaber, Samer M; Sullivan, Sarah; Margulies, Susan S (2015) Noninvasive metrics for identification of brain injury deficits in piglets. Dev Neuropsychol 40:34-9
Clevenger, Amy C; Kilbaugh, Todd; Margulies, Susan S (2015) Carotid artery blood flow decreases after rapid head rotation in piglets. J Neurotrauma 32:120-6

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