Authors :
Presenting Author: Md Adil ARMAN, BS – Florida International University
Pritom Kumar Saha, BS – Florida International University
Nija White, BS – Florida International University
Alexandra Fernandez, BS – Florida International University
Andres Garcia, BS – Florida International University
Oleksii Shandra, MD, PhD – Florida International University
Rationale:
Sleep disruption and traumatic brain injury (TBI) both contribute to post traumatic epilepsy (PTE) risk. TBI alone is a known cause of sleep disturbances and PTE and studies suggest sleep loss following TBI can intensify neuronal injury, resulting in more severe long term consequences, yet whether chronic sleep disruption before injury increases the risk of PTE has not been established. Among the biomarkers associated with epileptogenesis, fast ripples (250–500 Hz), particularly those coupled with delta oscillations, have been linked to epileptic seizures. Sleep disturbance contributes to cortical hyperexcitability and increased fast ripples in epilepsy, suggesting a mechanistic link between sleep and pathophysiology of epilepsy. Despite a thorough exploration of the relationship between sleep and epilepsy, data on the impact of sleep disruption on PTE remains sparse. Previously, we found a statistically significant increase in fast ripple numbers in animals that developed PTE, compared to those that did not after TBI. This reinforces our current focus on fast ripples as an early predictive biomarker of PTE. Current anti-epileptic drugs often worsen sleep, which can promote more seizures. Transcranial magnetic stimulation (TMS) is a promising non-invasive technique, but inconsistent effects on seizures highlight the need for standardization. This study hypothesizes that chronic sleep disruption promotes hyperexcitable networks intensifying injury-induced neuroplasticity and contributing to post-traumatic epileptogenesis. We also hypothesize that TMS may mitigate these effects by reducing hyperexcitability.
Methods:
12 to 16 weeks old male and female mice (n = 5) were randomly assigned into either a sleep disruption group or a no sleep disruption group. Sleep disruption was performed for 14 days with 2 minutes interval period. Following the last day of sleep disruption, mice were selected for either repetitive diffuse TBI (rdTBI) or SHAM injury and were subjected to stereotactic implantation of EEG electrodes with EMG wire leads. EEG recording was conducted continuously for 2 months to detect seizures, spikes, and fast ripples. Repetitive TMS was performed daily for 14 days beginning 24 hours after rdTBI. We conducted electroencephalographic analyses in MATLAB to assess the occurrence and coupling of fast ripples with physiological and pathological frequency bands, seizure activity, and spikes.
Results: Sleep-disrupted TBI mice showed over a 3-fold increase in fast ripple events compared to SHAM, while TMS treatment reduced fast ripples by 54.5% relative to untreated TBI, supporting its potential as a therapeutic modality for mitigating post-traumatic epilepsy risk. In addition, we observed significant group differences in power spectrum patterns, along with notable coupling of fast ripples with both delta and theta frequency bands.
Conclusions:
These findings highlight fast ripples as a key biomarker of sleep disrupted post-traumatic epileptogenesis and suggest that TMS may offer a promising strategy to suppress fast ripple associated hyperexcitability and reduce epilepsy risk.
Funding:
Department of Defense CDMRP #HT94252410116