The large strain mechanical properties of adult porcine gray and white matter brain tissues were measured in shear and confirmed in compression. Consistent with local neuroarchitecture, gray matter showed the least amount of anisotropy, and corpus callosum exhibited the greatest degree of anisotropy. Mean regional properties were significantly distinct, demonstrating that brain tissue is inhomogeneous. Fresh adult human brain tissue properties were slightly stiffer than adult porcine properties but considerably less stiff than the human autopsy data in the literature. Mixed porcine gray/white matter samples were obtained from animals at “infant” and “toddler” stages of neurological development, and shear properties compared to those in the adult. Only the infant properties were significantly different (stiffer) from the adult.

The mechanical properties of the adult human skull are well documented, but little information is available for the infant skull. To determine the age-dependent changes in skull properties, we tested human and porcine infant cranial bone in three-point bending. The measurement of elastic modulus in the human and porcine infant cranial bone agrees with and extends previous published data [McPherson, G. K., and Kriewall, T. J. (1980), J. Biomech., 13, pp. 9–16] for human infant cranial bone. After confirming that the porcine and human cranial bone properties were comparable, additional tensile and three-point bending studies were conducted on porcine cranial bone and suture. Comparisons of the porcine infant data with previously published adult human data demonstrate that the elastic modulus, ultimate stress, and energy absorbed to failure increase, and the ultimate strain decreases with age for cranial bone. Likewise, we conclude that the elastic modulus, ultimate stress, and energy absorbed to failure increase with age for sutures. We constructed two finite element models of an idealized one-month old infant head, one with pediatric and the other adult skull properties, and subjected them to impact loading to investigate the contribution of the cranial bone properties on the intracranial tissue deformation pattern. The computational simulations demonstrate that the comparatively compliant skull and membranous suture properties of the infant brain case are associated with large cranial shape changes, and a more diffuse pattern of brain distortion than when the skull takes on adult properties. These studies are a fundamental initial step in predicting the unique mechanical response of the pediatric skull to traumatic loads associated with head injury and, thus, for defining head injury thresholds for children. [S0148-0731(00)00904-3]

Object. Rotational loading conditions have been shown to produce subdural hemorrhage and diffuse axonal injury. No experimental data are available with which to compare the rotational response of the head of an infant during accidental and inflicted head injuries. The authors sought to compare rotational deceleration sustained by the head among free falls, from different heights onto different surfaces, with those sustained during shaking and inflicted impact. Methods. An anthropomorphic surrogate of a 1.5-month-old human infant was constructed and used to simulate falls from 0.3 m (1 ft), 0.9 m (3 ft), and 1.5 m (5 ft), as well as vigorous shaking and inflicted head impact. During falls, the surrogate experienced occipital contact against a concrete surface, carpet pad, or foam mattress. For shakes, investigators repeatedly shook the surrogate in an anteroposterior plane; inflicted impact was defined as the terminal portion of a vigorous shake, in which the surrogate's occiput made contact with a rigid or padded surface. Rotational velocity was recorded directly and the maximum (peak—peak) change in angular velocity and the peak angular acceleration were calculated. Analysis of variance revealed significant increases in the and associated with falls onto harder surfaces and from higher heights. During inflicted impacts against rigid surfaces, the and were significantly greater than those measured under all other conditions. Conclusions. Vigorous shakes of this infant model produced rotational responses similar to those resulting from minor falls, but inflicted impacts produced responses that were significantly higher than even a 1.5-m fall onto concrete. Because larger accelerations are associated with an increasing likelihood of injury, the findings indicate that inflicted impacts against hard surfaces are more likely to be associated with inertial brain injuries than falls from a height less than 1.5 m or from shaking.

Cyclosporin A (CsA) has been shown to be neuroprotective in mature animal models of traumatic brain injury (TBI), but its effects on immature animal models of TBI are unknown. In mature animal models, CsA inhibits the opening of the mitochondrial permeability transition pore (MPTP), thereby maintaining mitochondrial homeostasis following injury by inhibiting calcium influx and preserving mitochondrial membrane potential. The aim of the present study was to evaluate CsA's ability to preserve mitochondrial bioenergetic function following TBI (as measured by mitochondrial respiration and cerebral microdialysis), in two immature models (focal and diffuse), and in two different species (rat and piglet). Three groups were studied: injured+CsA, injured+saline vehicle, and uninjured shams. In addition, we evaluated CsA's effects on cerebral hemodynamics as measured by a novel thermal diffusion probe. The results demonstrate that post-injury administration of CsA ameliorates mitochondrial dysfunction, preserves cerebral blood flow (CBF), and limits neuropathology in immature animals 24 h post-TBI. Mitochondria were isolated 24 h after controlled cortical impact (CCI) in rats and rapid non-impact rotational injury (RNR) in piglets, and CsA ameliorated cerebral bioenergetic crisis with preservation of the respiratory control ratio (RCR) to sham levels. Results were more dramatic in RNR piglets than in CCI rats. In piglets, CsA also preserved lactate pyruvate ratios (LPR), as measured by cerebral microdialysis and CBF at sham levels 24 h after injury, in contrast to the significant alterations seen in injured piglets compared to shams (p<0.01). The administration of CsA to piglets following RNR promoted a 42% decrease in injured brain volume (p<0.01). We conclude that CsA exhibits significant neuroprotective activity in immature models of focal and diffuse TBI, and has exciting translational potential as a therapeutic agent for neuroprotection in children.