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Pathophysiological Response to Experimental Diffuse Brain Trauma Differs as a Function of Developmental Age

Cernak I.a, c · Chang T.a, b · Ahmed F.A.a, c · Cruz M.I.a · Vink R.e · Stoica B.a, d · Faden A.I.a, d
aDepartment of Neuroscience, Georgetown University Medical Center, and bPediatrics and Neurology, Children’s National Medical Center, Washington, D.C., cJohns Hopkins University Applied Physics Laboratory Biomedicine Business Area, National Security Technology Department, Laurel, Md., and dShock Trauma and Anesthesiology Research (STAR) Center, University of Maryland School of Medicine, Baltimore, Md., USA; eDepartment of Pathology, University of Adelaide, Adelaide, S.A., Australia Dev Neurosci 2010;32:442–453 (DOI:10.1159/000320085)

Abstract

The purpose of experimental models of traumatic brain injury (TBI) is to reproduce selected aspects of human head injury such as brain edema, contusion or concussion, and functional deficits, among others. As the immature brain may be particularly vulnerable to injury during critical periods of development, and pediatric TBI may cause neurobehavioral deficits, our aim was to develop and characterize as a function of developmental age a model of diffuse TBI (DTBI) with quantifiable functional deficits. We modified a DTBI rat model initially developed by us in adult animals to study the graded response to injury as a function of developmental age – 7-, 14- and 21-day-old rats compared to young adult (3-month-old) animals. Our model caused motor deficits that persisted even after the pups reached adulthood, as well as reduced cognitive performance 2 weeks after injury. Moreover, our model induced prominent edema often seen in pediatric TBI, particularly evident in 7- and 14-day-old animals, as measured by both the wet weight/dry weight method and diffusion-weighted MRI. Blood-brain barrier permeability, as measured by the Evans blue dye technique, peaked at 20 min after trauma in all age groups, with a second peak found only in adult animals at 24 h after injury. Phosphorus MR spectroscopy showed no significant changes in the brain energy metabolism of immature rats with moderate DTBI, in contrast to significant decreases previously identified in adult animals.

 

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