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Traumatic axonal injury after closed head injury in the neonatal pig
Ramesh Raghupathi1, Susan S Margulies
1Department of Neurosurgery, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Insights
Pediatric closed head injury, a major cause of child mortality, was modeled in piglets. Rapid head rotation without impact induced subarachnoid hemorrhage and traumatic axonal injury, mimicking injuries seen in children.
Area of Science:
- Biomedical Engineering
- Neuroscience
- Pediatric Traumatology
Background:
- Closed head injury is a primary cause of death and disability in children.
- Pathologies include diffuse axonal injury (DAI) and subarachnoid hematoma (SAH).
- Understanding the biomechanics of pediatric head injury requires appropriate animal models.
Purpose of the Study:
- To investigate the biomechanical factors of closed head injury in infants.
- To utilize a piglet model that mimics human infant brain development.
- To characterize the resulting brain injuries from inertial rotation.
Main Methods:
- Seven 3-5-day-old piglets were subjected to rapid, inertial head rotation.
- Animals were sacrificed 6 hours post-injury for analysis.
- Histological examination identified neurofilament protein accumulation indicative of traumatic axonal injury (TAI).
Main Results:
- Five of seven piglets experienced apnea and loss of reflexes post-injury.
- Subarachnoid hemorrhage (SAH) was observed in frontal lobes, cerebellum, and brainstem.
- TAI was evident in six of seven piglets, primarily in white matter tracts and the midbrain.
Conclusions:
- Inertial rotation of the piglet head without impact effectively models pediatric closed head injury.
- This model reliably induces SAH and TAI, consistent with injuries in children.
- The piglet model provides a valuable tool for studying the mechanisms of infant brain trauma.
Abstract:
Closed head injury is the leading cause of morbidity and mortality in infants and children, and results in pathologies such as diffuse axonal injury (DAI) and subarachnoid hematoma (SAH). To better understand the mechanical environment associated with closed head injury in the pediatric population, animal models that include salient features of human infant brain must be utilized. Based on detailed information regarding the parallels between brain development in the pig and the human, the 3-5-day-old piglet was used to represent the infant at less than 3 months of age. Anesthetized piglets (n = 7) were subjected to rapid, inertial (nonimpact) rotation of the head about its axial plane and sacrificed at 6 h postinjury. Immediately following injury, five of seven piglets were apneic, with an absence of pupillary and pain reflexes. All piglets exhibited severe coma immediately postinjury, but recovered by sacrifice time. Blood was present on the surface of the frontal lobes, cerebellum, and brainstem, and subarachnoid hemorrhage was evident in the frontal cortex. In six of seven brain-injured piglets, accumulation of the 68-kDa neurofilament protein was evident in contiguous axons (swollen) and occasionally in disconnected axons (axonal bulbs), suggestive of traumatic axonal injury (TAI). Mapping of the regional pattern of TAI revealed injured axons predominantly in central and peripheral white matter tracts in the frontal and temporal lobes and in the midbrain. The number of injured axons was equivalent in both hemispheres, and did not correlate to the load applied to the head. Together, these data demonstrate that rapid rotation of the piglet head without impact results in SAH and TAI, similar to that observed in children following severe brain trauma.