Scaled cortical impact in immature swine: effect of age and gender on lesion volume

Abstract

The piglet scaled cortical impact model creates a focal contusion using a skull-mounted, spring-loaded blunt indentation device scaled to achieve identical tissue strains in subjects with different brain sizes. Preliminary data showed that contusion size increased proportional to subject age. This study details the results from a new, larger series of subjects of three ages, and compares the effect of age and additional host and physiologic variables on injury response. Sixty-seven subjects, including infant (5- to 7-day-old), "toddler" (1-month-old), and early adolescent (4-month-old) swine underwent scaled cortical impact under strict anesthetic protocols. Serum glucose, testosterone, and 17beta-estradiol levels were measured. Lesion size was measured at 1 week post injury, as the ratio of the lesion area over the area of the contralateral hemisphere. Adolescent subjects had lesions over eight times larger than infants (p < 0.0001). Lesion volumes were larger in toddlers than in infants, most significantly for males (p < 0.05). Adolescent subjects were warmer on average, but there was no correlation between temperature and lesion volume within any age group. Serum glucose did not differ among ages. Infant males had the highest levels of circulating sex steroids. In this model, age was the most robust predictor of lesion size. Temperature had an effect, but did not explain all the variability seen among age groups. There was an interaction among gender, hormone levels, and lesion size in younger subjects. Characterization of these variables allows use of this model for treatment trials for subjects at different stages of maturation.

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

“…Although the response of the infant brain has been shown to be distinct from that of adolescents and adults, experimental studies that have focused on differences between the infant and toddler offer disparate evidence for the effect of maturation on injury response. Specifically, porcine focal lesion traumatic brain injury (TBI) models have demonstrated that geometricallyscaled cortical contusions produce smaller lesions at 1 week and 30 days post-injury in the infant than in the toddler (Duhaime et al, , 2003Missios et al, 2009), but that infant piglets may sustain larger decreases in cerebral blood flow (Armstead and Kurth, 1994) in the first 3 h following TBI than toddler piglets. Rodent models have shown that infant-age animals are more susceptible to apoptotic neurodegeneration in the initial 6-24 h immediately following mass-scaled weight drops (Bittigau et al, 1999), chronic cognitive deficits several weeks after injury , but similar white matter damage following contusive brain injury than toddler-age animals.…”

Development of a Model of Hemispheric Hypodensity (“Big Black Brain”)

“…We used our wellcharacterized cortical impact model to induce mechanical trauma, as children with HH often have evidence of blunt mechanical trauma of some type. 6,22,23 Our cortical impact is reproducible and injures both gray and white matter. 24 We also induced mass effect, apnea, hypoventilation, and seizures to assess the role of these insults.…”

“…23,25 The brain was removed leaving the ventral dura intact and post-fixed at 4°C for up to 1 month. The eyes with attached optic nerves were removed by dissection through the floor of the anterior cranial fossa into the orbital space to expose the globe and contents of the orbit in a subset of injured piglets (n = 3).…”