Early Electrographic Biomarkers for Epilepsy in a Mouse Model of Repetitive Diffuse Traumatic Brain Injury
Abstract number :
3.221
Submission category :
2. Translational Research / 2C. Biomarkers
Year :
2024
Submission ID :
220
Source :
www.aesnet.org
Presentation date :
12/9/2024 12:00:00 AM
Published date :
Authors :
Presenting Author: MD ADIL ARMAN, – Florida International University
Pritom Kumar Saha, BS – Florida International University
Biswajit Maharathi, PhD – University of Illinois at Chicago
Stefanie Robel, PhD – University of Alabama at Birmingham
Oleksii Shandra, MD,PhD – Florida International University
Rationale:
Post-traumatic epilepsy (PTE) remains a major public health challenge. To date, all therapies are symptomatic, and injury severity remains the most common factor in assessing individuals at risk of developing PTE. This lack of accurately defined and reliable biomarkers of post-traumatic epileptogenesis, challenges stratifying which individuals should receive treatment or be monitored further. We hypothesized that longitudinal, automated power spectrum analysis of continuous EEG data may identify the signatures of post-traumatic epileptogenesis and its onset in mice after repetitive diffuse traumatic brain injury (rdTBI).
Methods:
We induced rdTBI in 12–16-week-old male mice using an impact acceleration model, mimicking key features of human non-lesional TBI. Continuous video-EEG monitoring for up to 4 months post-TBI assessed seizure onset and power spectrum changes, comparing TBI mice with sham controls. To identify the qualitative and quantitative power spectrum signatures of post-traumatic epileptogenesis, we used a semi-automated algorithm to analyze different frequency bands' power and phase-amplitude coupling.
Results:
After rdTBI, 7 out of 28 mice (25%) developed spontaneous, recurrent, chronic seizures with an average onset at 2 months post-TBI. Our analysis revealed significant EEG power spectrum differences between TBI, PTE, and Sham groups. Mice that developed seizures(PTE+) had lower delta, theta, alpha, beta, gamma, relative alpha variability, alpha to delta ratio, and overall power than the other groups for the first 2 weeks. These differences were transient, with no significant differences beyond this period. These findings highlight early neurophysiological disruptions, crucial for identifying early electrographic biomarkers and the onset of PTE. PTE+ mice exhibited significantly increased high-frequency oscillations(HFO,80-250 Hz) and pathological high-frequency oscillations(pHFO,250-500 Hz). The higher occurrence of HFO and pHFO in PTE+ animals reflect focal and network hyperexcitability, associated with epileptogenic activity. Importantly, we identified delta-coupled pHFO in PTE animals, which precede epileptic seizures. Identifying these patterns before seizure onset is crucial for early intervention during the latent period before PTE development.
Conclusions:
Our study shows that PTE+ mice have distinct EEG power spectrum changes identifiable within the first two weeks of the latent phase post-rdTBI, before seizures. We demonstrate that pHFO in the cortex can be accurately identified using epidural screw electrodes and that these pHFOs are closely linked to delta oscillations through phase-amplitude coupling. We observed that all 7/7(100%) PTE+ mice had at least one seizure during light hours, with 3/7(42.86%) having seizures exclusively during light hours and 1/7(14.28%) having 18(72%) of 25 seizures during light hours. Our data suggest potential circadian seizure patterns and sleep-wake-related pathophysiology. These findings emphasize the translational significance of our data as potential biomarkers that may improve diagnostics and identify therapeutic windows for preventive strategies after TBI.
Funding: CURE#488554, CDMRP#HT94252410116
Translational Research