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Published on: June 5, 2019
Repeated traumatic brain injury affects composite cognitive function in piglets
Stuart H Friess1, Rebecca N Ichord, Jill Ralston
1Department of Anesthesiology and Critical Care Medicine, The Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Insights
Repetitive mild head trauma in infants can cause significant cognitive deficits and white matter injury. The timing of injuries is critical, with injuries closer together leading to worse outcomes and higher mortality.
Area of Science:
- Neuroscience
- Pediatric Traumatology
- Neuropathology
Background:
- The cumulative effects of repetitive mild head injuries in children are not well understood.
- Mild traumatic brain injury (mTBI) can lead to long-term cognitive and neurological deficits.
- Neonatal head trauma is a significant concern in pediatric critical care.
Purpose of the Study:
- To investigate the neuropathological and neurobehavioral effects of repetitive mild head injuries in a neonatal animal model.
- To develop a cognitive composite dysfunction score to assess the impact of head trauma.
- To determine if the interval between injuries influences outcome severity.
Main Methods:
- Neonatal piglets (3-5 days old) were subjected to single or double moderate axial head rotations (190 rad/s) with varying intervals (24 hours or 7 days).
- Neurobehavioral assessments evaluated executive function, memory, learning, and problem-solving abilities.
- White matter injury was quantified using beta-amyloid precursor protein (beta-APP) staining.
- A cognitive composite dysfunction score was developed and correlated with injury severity.
Main Results:
- Animals with two head rotations 24 hours apart exhibited a 43% mortality rate and poorer problem-solving skills compared to shams.
- White matter injury was significantly higher in the group with injuries 7 days apart compared to single injury and sham groups.
- Worsening cognitive composite scores correlated with increased white matter axonal injury severity.
- Two head rotations resulted in poorer neuropathological and neurobehavioral outcomes than single rotations.
Conclusions:
- Repetitive head rotations in immature animals lead to worse outcomes than single events.
- The interval between head injuries significantly impacts mortality and injury severity, with closer intervals being more detrimental.
- Findings have critical implications for understanding and managing infants subjected to repeated inflicted head trauma.
Abstract:
Cumulative effects of repetitive mild head injury in the pediatric population are unknown. We have developed a cognitive composite dysfunction score that correlates white matter injury severity in neonatal piglets with neurobehavioral assessments of executive function, memory, learning, and problem solving. Anesthetized 3- to 5-day-old piglets were subjected to single (n = 7), double one day apart (n = 7), and double one week apart (n = 7) moderate (190 rad/s) rapid non-impact axial rotations of the head and compared to instrumented shams (n = 7). Animals experiencing two head rotations one day apart had a significantly higher mortality rate (43%) compared to the other groups and had higher failures rates in visual-based problem solving compared to instrumented shams. White matter injury, assessed by beta-APP staining, was significantly higher in the double one week apart group compared to that with single injury and sham. Worsening performance on cognitive composite score correlated well with increasing severity of white matter axonal injury. In our immature large animal model of TBI, two head rotations produced poorer outcome as assessed by neuropathology and neurobehavioral functional outcomes compared to that with single rotations. More importantly, we have observed an increase in injury severity and mortality when the head rotations occur 24 h apart compared to 7 days apart. These observations have important clinical translation to infants subjected to repeated inflicted head trauma.
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