Abstracts

Rationale: About 20% of traumatic brain injury (TBI) patients develop post-traumatic epilepsy. There is an urgent need for biomarkers to facilitate the diagnosis of post-traumatic epileptogenesis. Multicenter-based preclinical studies can facilitate the discovery and testing of clinically relevant biomarkers. Our objective here is to standardize the protocol of lateral fluid-percussion injury (FPI) model production for a multicenter-based approach on biomarkers studies of post-traumatic epileptogenesis. Methods: Three international sites from the international multicenter-based project, Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx), were involved: The University of Eastern Finland (Site 1), Monash University (Site 2) and Regents of the University of California, Los Angeles (Site 3). Adult male Sprague Dawley rats were used in all the sites. The animals were divided into two groups, TBI or sham-injured groups. TBI was induced using the lateral FPI model. Data on injury parameters including hit pressure, duration of post-impact apnea, time to right, occurrence of post-impact seizure and severity of the acute functional impairment was collected and compared between the sites. Results: The mean weight of the animals at the beginning of the experiment was 344 ± 2.1 g (n = 119), 353 ± 30 g (n = 78) and 322 ± 3.6 g (n = 81) for site 1 to 3 respectively. The mean hit pressure differed between the sites, 2.85 ± 0.02 atm, (n = 99), 2.59 ± 0.03 atm (n = 53) and 2.42 ± 0.03 atm (n = 58) (p<0.001) for site 1 to 3 respectively. Furthermore, the sites differed in the duration of post-impact apnea 33.7 ± 1.5 s, 63.6 ± 10.8 s, and 33.73 ± 3.2 s (p<0.01); and the duration to right after impact 1014 ± 54.9 s, 1613 ± 191.1 s, 917 ± 71.9 s (p<0.05), for site 1 to 3 respectively. However, the acute functional impairment as assessed with the neuroscore on day 2 post-injury was similar between the sites 12 ± 0.6 (site 1), 13 ± 2.0 (site 2), 12 ± 0.4 (site 3). Post-impact seizures were observed in 48.5% (48/99), 16.3% (8/46) and 1.7% (1/63) of animals in site 1, 2 and 3 respectively (p<0.0001). Moreover, the acute (<72 h) post-impact mortality was 16.8% (17/101) (site 1), 35.5% (22/62) (site 2) and 57.1% (36/63) (site 3) (p<0.0001). Conclusions: Despite differences in the injury parameters, the severity of the acute functional impairment did not differ significantly between the study sites, suggesting that the lateral fluid-percussion brain injury is relatively similar. Furthermore, significant variability was also seen in post-impact seizures and mortality. Variability in the injury parameters is probably related to differences in technical manipulations and internal settings. Funding: Supported by NINDS Center without Walls, U54 NS100064 (EpiBioS4Rx)