Abstract
Objective
To assess reproducibility of the epilepsy outcome and phenotype in lateral fluid-percussion model of post-traumatic epilepsy across three study sites.
Methods
A total of 525 adult male Sprague-Dawley rats were randomized to lateral fluid-percussion -induced brain injury (FPI) or sham-operation. Of these, 264 were assigned to magnetic resonance imaging (MRI cohort, 43 sham, 221 TBI) and 261 for electrophysiological follow-up (EEG cohort, 41 sham, 220 TBI). A major effort was made to harmonize the rats, materials, equipment, procedures and monitoring systems. On the 7th post-TBI month, rats were video-EEG monitored for for epilepsy diagnosis.
Results
A total of 245 rats were video-EEG phenotyped for epilepsy on the 7th post-injury month (121 in MRI cohort, 124 in EEG cohort). In the whole cohort (n=245), the prevalence of PTE in rats with TBI was 22%, being 27% in the MRI and 18% in the EEG cohort (p>0.05). Prevalence of PTE did not differ between the three study sites (p>0.05). The average seizure frequency was 0.317 ± 0.725 seizures/d in UEF (Finland), 0.085 ± 0.067 in Monash (Australia) and 0.299 ± 0.266 in UCLA (USA)(p<0.01 as compared to Monash). The average seizure duration did not differ between the UEF (104 ± 48 s), Monash (90 ± 33 s) and UCLA (105 ± 473 s)(p>0.05). Of the 219 seizures, 53% occurred as part of a seizure cluster (≥3 seizures/24 h)(p<0.05 between the study sites). Of the 209 seizures, 56% occurred during lights-on period and 44% during lights-off period (p>0.05 between the study sites).
Significance
The PTE phenotype induced by lateral FPI is reproducible in a multi-center design. Our study supports the feasibility of performing pre-clinical multicenter trials in PTE to increase statistical power and experimental rigor to produce clinically translatable data to combat epileptogenesis after TBI.
DIC