Abstracts

Rationale: For most individuals, the risk of epilepsy after a mild traumatic brain injury (mTBI) is small (1.5-2.2-fold). However, mTBI patients with a first degree relative with epilepsy have a substantially greater (5.8-fold) risk. Approximately 9.3% of individuals have a first degree relative with epilepsy and thus, given the high mTBI prevalence, it is necessary to elucidate mechanisms by which mTBI may produce seizures in these susceptible individuals.

Methods: Experiments were performed with our previously described mice that heterozygously (Het) express a human epilepsy gene mutation (Gabra1(A322D)) as well as their wild type (WT) littermates. We used 1) continuous two electrode EEG monitoring and 2) 16 channel high density EEG (HdEEG) recordings to determine the interactions of mTBI and genotype on seizure incidence and cortical networks, respectively. WT and Het mice were implanted with EEG or HdEEG electrodes and subjected to a 24-hour baseline video-EEG/HdEEG recording. Mice then received either a single 40 psi closed-skull overpressure mTBI or sham exposure to the mTBI apparatus. After mTBI/sham, the mice underwent subsequent EEG/HdEEG recordings for the occurrence of early seizures (< 1 week post injury). A linear mixed effect model was used to determine the association of the fixed effects (genotype and mTBI/sham) on seizure incidence. Time frequency transforms were performed on the HdEEG recordings and cluster-based permutation tests were used to determine the effects of mTBI on resting state and ictal cortical activity. Using intra-HdEEG-electrode weighted phase lag indices, we determined the effects of mTBI on resting state and ictal network node degree.

Results: In Het mice, mTBI increased early post-injury seizures by 1.9 ± 0.2-fold (P < 0.05). There was no effect of mTBI on seizures in WT mice or sham exposure in Het mice. In Het mice, mTBI increased resting state and decreased ictal theta spectral density in cortical regions overlying somatosensory and visual cortices (P < 0.05). In addition, mTBI decreased resting state, but increased ictal delta/theta frequency network node degree in similar cortical regions (P < 0.05).