A perfect storm: The distribution of tissue damage depends on seizure duration, hemorrhage, and developmental stage in a gyrencephalic, multi-factorial, severe traumatic brain injury model

Abstract

The pathophysiology of extensive cortical tissue destruction observed in hemispheric hypodensity, a severe type of brain injury observed in young children, is unknown. Here, we utilize our unique, large animal model of hemispheric hypodensity with multifactorial injuries and insults to understand the pathophysiology of this severe type of traumatic brain injury, testing the effect of different stages of development. Piglets developmentally similar to human infants (1 week old, “infants”) and toddlers (1 month old, “toddlers”) underwent injuries and insults scaled to brain volume: cortical impact, creation of mass effect, placement of a subdural hematoma, seizure induction, apnea, and hypoventilation or a sham injury while anesthetized with a seizure-permissive regimen. Piglets receiving model injuries required overnight intensive care. Hemispheres were evaluated for damage via histopathology. The pattern of damage was related to seizure duration and hemorrhage pattern in “toddlers” resulting in a unilateral hemispheric pattern of damage ipsilateral to the injuries with sparing of the deep brain regions and the contralateral hemisphere. While “infants” had the equivalent duration of seizures as “toddlers”, damage was less than “toddlers”, not correlated to seizure duration, and was bilateral and patchy as is often observed in human infants. Subdural hemorrhage was associate with adjacent focal subarachnoid hemorrhage. The percentage of the hemisphere covered with subarachnoid hemorrhage was positively correlated with damage in both developmental stages. In “infants”, hemorrhage over the cortex was associated with damage to the cortex with sparing of the deep gray matter regions; without hemorrhage, damage was directed to the hippocampus and the cortex was spared. “Infants” had lower neurologic scores than “toddlers”. This multifactorial model of severe brain injury caused unilateral, wide-spread destruction of the cortex in piglets developmentally similar to toddlers where both seizure duration and hemorrhage covering the brain were positively correlated to tissue destruction. Inherent developmental differences may affect how the brain responds to seizure, and thus, affects the extent and pattern of damage. Study into specifically how the “infant” brain is resistant to the effects of seizure is currently underway and may identify potential therapeutic targets that may reduce evolution of tissue damage after severe traumatic brain injury.

Abusive Head Trauma in Infants During the COVID-19 Pandemic in the Paris Metropolitan Area

“…Indeed, these studies compared the incidence of CAN or AHT during the second and/or third quarter of 2020 with the prepandemic period but did not explore the incidence of AHT in 2021, making it impossible to assess the medium-term consequences of the pandemic and the mitigation measures taken. The increase in mortality could be explained by an increased delay between the trauma and the first medical examination, leading to untreated seizures and additional brain damage . Moreover, none of these previous studies was population-based, thus failing to consider every case of CAN.…”

Release of extracellular matrix components after human traumatic brain injury

“…This pilot study will hopefully lay the groundwork for larger clinical studies by presenting the concentrations and distributions of the sGAGs and disaccharides present within the ventricular CSF and plasma in a two-center group of severely injured trauma patients. Addressing the mechanistic questions raised by this observational clinical study may best be accomplished using experimental preparations 37 in which both intra and extracellular sGAG levels can be analyzed after controlled subtypes of traumatic brain injury. (GRAPH 3) caption: Plasma and CSF sGAG concentrations (ng/ml) of chondroitin sulfate plotted against one another and separated into groups denoting isolated head trauma or multitrauma.…”

Robust, Long-Term Video EEG Monitoring in a Porcine Model of Post-Traumatic Epilepsy

“…Acute EEG recordings in anesthetized swine after various brain insults are relatively simple and are well established ( Costine-Bartell, Price et al, 2021 ), but recording EEGs in awake and restrained and/or tethered swine over the course of several days is more difficult. The standard of EEG in PTE in rodent models of TBI is tethered EEG ( Shandra and Robel, 2020 ) or radiotelemetric EEG ( White, Williams et al, 2010 ).…”