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 17b-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.

Traumatic Brain Injury Elicits Similar Alterations in α7 Nicotinic Receptor Density in Two Different Experimental Models

“…Despite the postulated enhanced capacity for functional recovery, the immature brain appears to be more vulnerable to injuries, at least after severe injury in humans (Feickert et al 1999;Mazzola and Adelson 2002), with potentially more drastic consequences for the cognitive development (Koskiniemi et al 1995). However, a recent experimental study with pigs of different age showed that the size of a cortical lesion increases with age (Missios et al 2009). Therefore, in experimental studies on immature TBI, the age of the animals is an important factor, because it determines roughly the comparable age group of children.…”

Neuroblast Distribution after Cortical Impact Is Influenced by White Matter Injury in the Immature Gyrencephalic Brain

“…Surgery and anesthesia protocols were employed as previously described (Missios et al, 2009 ; Costine et al, 2015 ). Briefly, on PND 7, anesthesia was induced and maintained with isoflurane mixed with room air and piglets were mechanically ventilated.…”

“…Briefly, on PND 7, anesthesia was induced and maintained with isoflurane mixed with room air and piglets were mechanically ventilated. Piglets received buprenorphine (0.005 mg/kg, IM), and heart rate, blood pressure, end tidal CO 2 , oxygen saturation, and body temperature were monitored and maintained within a narrow range (Missios et al, 2009 ). As previously described, a craniectomy to create a 2 cm burr hole in the skull was performed over the right coronal suture exposing the rostral gyrus, the somatosensory cortex with somatotopy to the snout (Missios et al, 2009 ).…”

“…Piglets received buprenorphine (0.005 mg/kg, IM), and heart rate, blood pressure, end tidal CO 2 , oxygen saturation, and body temperature were monitored and maintained within a narrow range (Missios et al, 2009 ). As previously described, a craniectomy to create a 2 cm burr hole in the skull was performed over the right coronal suture exposing the rostral gyrus, the somatosensory cortex with somatotopy to the snout (Missios et al, 2009 ). This site was chosen to create a pathologically significant, but clinically silent lesion that we have previously characterized (Duhaime et al, 2000 , 2003 ; Missios et al, 2009 ).…”

“…In our large animal model, cortical impact affects both cortical gray matter and cerebral white matter as it deforms 50% of the distance from the cortical gyral crest to the lateral ventricles and thus models blunt impact head injury in children who have deformable skulls and display preferential white matter injury (Duhaime et al, 2000 ; Missios et al, 2009 ). We have previously demonstrated an increase in lesion size with increasing age despite injury input parameters scaled for brain growth, and have demonstrated a developmental decrease in the area of the SVZ with increasing age (Costine et al, 2015 ).…”