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Shaking Up Our Approach: The Need for Characterization and Optimization of Pre-clinical Models of Infant Abusive Head
Sydney Harris1, Holly R Chinnery2, Bridgette D Semple1,3,4
1Department of Neuroscience, Monash University, Melbourne, Victoria, Australia.
Insights
Abusive head trauma (AHT) is a severe infant injury. This review examines AHT diagnosis, pathology, and animal models, highlighting research gaps and treatment opportunities for better child development.
Area of Science:
- Pediatric Neurology
- Neuroscience
- Public Health
Background:
- Abusive head trauma (AHT) is a leading cause of death and disability in infants, often resulting from inflicted injuries by caregivers.
- Repetitive AHT poses a significant burden, underscoring the need for better understanding and prevention strategies.
Purpose of the Study:
- To review the clinical diagnosis, symptoms, prognosis, and neuropathology of AHT.
- To evaluate existing animal models of AHT and define criteria for an ideal model.
- To identify knowledge gaps and opportunities in pre-clinical AHT research and consider potential treatments.
Main Methods:
- Literature review of clinical data, neuropathology, and existing animal models of AHT.
- Comparative analysis of AHT with other injury models (e.g., repetitive mild TBIs, hypoxic-ischemic injuries).
- Discussion of developmental milestones in vulnerable infants and potential therapeutic interventions.
Main Results:
- AHT presents unique diagnostic and neuropathological challenges, particularly with repetitive injuries.
- Current animal models have limitations in fully recapitulating the complexities of human AHT.
- Insights from related injury models suggest avenues for future pre-clinical research.
Conclusions:
- Optimized, well-characterized animal models are crucial for advancing AHT research.
- Further investigation is needed to understand the long-term neuropathological and neurobehavioral consequences of AHT.
- Developing effective treatments is essential to improve outcomes for affected children.
Abstract:
Traumatic brain injuries (TBIs) are a large societal and individual burden. In the first year of life, the vast majority of these injuries are the result of inflicted abusive events by a trusted caregiver. Abusive head trauma (AHT) in infants, formerly known as shaken baby syndrome, is the leading cause of inflicted mortality and morbidity in this population. In this review we address clinical diagnosis, symptoms, prognosis, and neuropathology of AHT, emphasizing the burden of repetitive AHT. Next, we consider existing animal models of AHT, and we evaluate key features of an ideal model, highlighting important developmental milestones in children most vulnerable to AHT. We draw on insights from other injury models, such as repetitive, mild TBIs (RmTBIs), post-traumatic epilepsy (PTE), hypoxic-ischemic injuries, and maternal neglect, to speculate on key knowledge gaps and underline important new opportunities in pre-clinical AHT research. Finally, potential treatment options to facilitate healthy development in children following an AHT are considered. Together, this review aims to drive the field toward optimized, well-characterized animal models of AHT, which will allow for greater insight into the underlying neuropathological and neurobehavioral consequences of AHT.
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