Maturation-dependent response of the piglet brain to scaled cortical impact

Abstract

Object. The goal of this study was to investigate the relationship between maturational stage and the brain's response to mechanical trauma in a gyrencephalic model of focal brain injury. Age-dependent differences in injury response might explain certain unique clinical syndromes seen in infants and young children and would determine whether specific therapies might be particularly effective or even counterproductive at different ages.Methods. To deliver proportionally identical injury inputs to animals of different ages, the authors have developed a piglet model of focal contusion injury by using specific volumes of rapid cortical displacement that are precisely scaled to changes in size and dimensions of the growing brain. Using this model, the histological response to a scaled focal cortical impact was compared at 7 days after injury in piglets that were 5 days, 1 month, and 4 months of age at the time of trauma. Despite comparable injury inputs and stable physiological parameters, the percentage of hemisphere injured differed significantly among ages, with the youngest animals sustaining the smallest lesions (0.8%, 8.4%, and 21.5%, for 5-day-, 1-month-, and 4-month-old animals, respectively, p = 0.0018).Conclusions. These results demonstrate that, for this particular focal injury type and severity, vulnerability to mechanical trauma increases progressively during maturation. Because of its developmental and morphological similarity to the human brain, the piglet brain provides distinct advantages in modeling age-specific responses to mechanical trauma. Differences in pathways leading to cell death or repair may be relevant to designing therapies appropriate for patients of different ages.

Maturation-dependent response of neurogenesis after traumatic brain injury in children

“…Furthermore, infant piglets had smaller lesions in response to scaled focal cortical impact than did toddler and adolescent piglets, but a greater total axonal lesion volume was observed at this same age compared with that in older piglets in response to angular deceleration. 17,18,58,64 Differences in study designs make it difficult to extrapolate the effect of trauma on humans with regard to neurogenesis and the ability to innately repair damaged tissue. Rates of neuronal migration under normal conditions in the human brain have yet to be determined, but we can expect, given the long distances involved, that it would take a long time for migrating neuroblasts to travel to a focal site of injury in humans.…”

Physiological and Pathological Responses to Head Rotations in Toddler Piglets

“…H ead trauma in toddler-age children is generally marked by a pattern of neural tissue injury and time course that are distinct from adults and even infants (Bruce, 1990;Duhaime et al, 2000). This is likely the result of changes in the central nervous system as it undergoes a period of accelerated growth and development.…”

Influences of Developmental Age on the Resolution of Diffuse Traumatic Intracranial Hemorrhage and Axonal Injury

“…In addition, these animals displayed a differing evolution of secondary injury where five-day-old piglets had earlier peak lesion volumes that resolved more quickly than four-week-old piglets. 18,19 These studies in focal brain injury demonstrate that the time course of secondary injury can be influenced by age at the time of injury.…”

“…3,[8][9][10][11][12][13][14][15][16][17][18][19] During the first four years of life, numerous cerebral developmental changes occur, which may contribute to these differences within the pediatric population, including continued myelination, changes in cerebrovascular tone, and increases in both brain size and neurotransmitter density. [20][21][22] Experimental studies of the age-dependent response to a scaled cortical impact found larger lesion volumes at seven days and one month post-TBI in four-week-old piglets, compared with five-dayold piglets.…”