Infant Abusive Head Trauma Induces Seizures and Cellular Stress in a Pre-Clinical Mouse Model

Abstract

Abusive head trauma (AHT) occurs when a child is grasped and shaken with such force that the brain moves within the skull. AHTs are not isolated events; repetition occurs in 30–50% of cases, with affected children experiencing ∼10 episodes. While many AHTs appear asymptomatic, there is often underlying cellular and neurological damage. Notably, seizures following AHT may be solely electrographic without overt behavioral signs and detectable only via electroencephalography (EEG). Thus, we examined electrographic seizures and indicators of cell stress in a mouse model of repeat AHT. On postnatal day (P)8, mice underwent hippocampal electrode surgery. On P10–12, 5 min of baseline EEG was recorded, followed by an AHT and 15 min of postinjury EEG recording. AHTs were modeled by securing a mouse to a shaking device at 400 rpm (5g) for 60 s. Sham mice underwent the same surgery and EEG recording procedures but were placed on the shaking device while it remained stationary. A separate cohort of mice forewent surgery but were exposed to the same AHT procedure and were euthanized on P21 or P45 for gene expression and telomere length (TL) analysis. Electrographic seizures occurred following 35.7% of AHTs, while no sham mice exhibited electrographic seizures. Repetitive AHTs affected gene expression in the hippocampus and olfactory bulbs, in genes related to cell stress (TERT, Sod1, P53, Drd2, Dnmt3a, iNOS), and TL at P21. These findings suggest that despite the absence of observable behavioral deficits, repeat AHTs result in measurable cellular damage and electrographic seizure activity.