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Published on: October 26, 2013
Pediatric Traumatic Brain Injury and Microvascular Blood-Brain Barrier Pathology
Josie L Fullerton1, Jennifer Hay2, Charlotte Bryant-Craig3
1School of Cardiovascular & Metabolic Health, University of Glasgow, Glasgow, United Kingdom.
Insights
Pediatric traumatic brain injury (TBI) shows distinct microvascular pathology, unlike adults, contributing to diffuse brain swelling. This autopsy study highlights age-dependent vascular differences in TBI outcomes.
Area of Science:
- Neuropathology
- Pediatric Traumatic Brain Injury
- Vascular Biology
Background:
- Pediatric traumatic brain injury (TBI) carries a higher risk of severe outcomes than adult TBI.
- The biological basis for adverse outcomes in pediatric TBI is not well understood.
- Diffuse brain swelling and second impact syndrome are concerns in pediatric TBI.
Purpose of the Study:
- To compare neuropathological findings of brain swelling and blood-brain barrier (BBB) disruption in pediatric versus adult TBI.
- To investigate age-dependent differences in vascular pathology following acute TBI.
Main Methods:
- Retrospective case series of autopsy material from the Glasgow TBI Archive.
- Inclusion of pediatric (3-18 years) and adult (≥19 years) patients with moderate or severe acute TBI.
- Histological evaluation of brain tissue for markers of endothelial cells (CD34) and BBB integrity (fibrinogen, IgG).
Main Results:
- Brain swelling was more frequently diffuse and bilateral in pediatric patients (83%) compared to adults (34%).
- Blood-brain barrier (BBB) disruption was prevalent in both groups (pediatric 80%, adult 91%).
- In pediatric TBI, BBB disruption primarily occurred at the microvascular, capillary level (84.7%), unlike in adults (31.2%).
Conclusions:
- Autopsy findings reveal age-dependent differences in vascular pathology after TBI.
- Pediatric TBI exhibits distinct microvascular BBB disruption, potentially contributing to diffuse brain swelling.
- Further research is needed to explore this microvascular pathology in pediatric TBI.
Importance:
Pediatric traumatic brain injury (TBI) is a major cause of morbidity and mortality, with an increased risk of catastrophic outcome compared with adult TBI, including diffuse brain swelling and so-called second impact syndrome. Nevertheless, the biological substrates driving adverse outcomes in pediatric TBI remain poorly described.
Objective:
To compare neuropathological evidence of brain swelling and blood-brain barrier (BBB) disruption after moderate or severe acute TBI in adult vs pediatric case material.
Design, Setting, And Participants:
In this retrospective case series, cases of pediatric (aged 3-18 years) and adult (aged ≥19 years) TBI were accrued from January 1, 1979, to December 31, 2005, and underwent laboratory-based assessment of autopsy material from the Glasgow TBI Archive. Data analysis was performed from January 2019 to January 2024.
Exposures:
Single moderate or severe TBI.
Main Outcomes And Measures:
Evaluation of representative brain tissue sections stained for markers of endothelia (CD34) and BBB integrity (fibrinogen and immunoglobin G).
Results:
Eighty-one pediatric patients (mean [SD] age, 12.1 [4.6] years; 50 [62%] male) and 62 adult patients (mean [SD] age, 38.7 [12.9] years; 35 [56%] male) were studied. At autopsy, when present, brain swelling was more often diffuse and bilateral among pediatric patients (64 of 81 cases [83%]) when compared with adult patients (21 of 62 [34%]) (P < .001). Histologic evidence of BBB disruption was common in material from both adult (57 of 62 [91%]) and pediatric (65 of 81 [80%]) (P = .06) patients. In pediatric patients, however, this was a predominantly microvascular, capillary-level pathology, which was a less common finding in adult case material (mean [SD], 84.7% [8.6%] vs 31.2% [7.7%]; P < .001).
Conclusions And Relevance:
This autopsy case series of patients dying in the acute phase after single moderate or severe TBI provides neuropathological evidence of age-dependent differences in vascular pathology. Specifically, although BBB disruption in pediatric material was typically confined to microvascular, capillary-level vessels, in adult case material, BBB disruption more typically involved larger-diameter vessels. This observation of distinct microvascular pathology in pediatric acute TBI requires further investigation. In the meantime, this study presents an intriguing potential candidate pathology contributing to diffuse brain swelling in this age group.
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