Abstracts

Rationale: Post-traumatic epilepsy (PTE) can be a significant cause of disability for TBI individuals. Therefore, it is necessary to develop biomarkers to establish appropriate syndromic diagnosis. In the present study, changes in electroencephalography (EEG), behavior and blood serum proteins were investigated in rat TBI model, to check if any of the above could serve as a biomarker for PTE.  Methods: Adult male Sprague-Dawley rats (n=9) were exposed to fluid percussion injury followed by EEG recordings with a combination of 16 microelectrodes implanted in adjacent areas of TBI and other brain areas. The data were analyzed for the presence of interictal spikes and seizures. Concurrently, anxiety level and memory were tested once a week and blood serum analysis for 4-hydroxynonenal (HNE-4), Matrix Metalloproteinase-9 (MMP-9) and Aquaporin-4 (AQP-4) were done during the 1st and the 2nd week after TBI. Based on EEG data, the animals were separated into ones, that became epileptic (E+) and ones that did not turn epileptic (E-). Rate of high frequency oscillations (HFOs), level of anxiety, memory and blood serum proteins were compared between E+ and E- groups, before and after TBI.  Results: 30% percent of rats became epileptic (E+), 70% did not (E-). The rate of HFOs increased in the prefrontal cortex and hippocampus areas in the E+ group within the first two weeks, but not in the E- group. 100% of rats in the E+ and 80% in the E- showed a decline in memory; 2, 12 and 24 weeks after TBI. We found 100% in the E+ group performed poorly in the anxiety-related behavior test; 2, 12 and 24 weeks after TBI. Only 50% of rats in the E- group showed an increase in anxiety in the second week. Blood serum analysis showed up-regulation of MMP-9 in 100% of rats in both the E+ and E- groups within the 1st and 2nd week after TBI. AQP-4 decreased in 70% of E+ rats and 100% in E- rats. Blood HNE-4 increased in all the rats in the E+ group within week 1 and in just 30% in E-. No changes were detected in the 2nd week in either of the group. Conclusions: The increased rate of HFOs is a stable biomarker of epileptogenesis after TBI. Our data suggests an increase in anxiety and blood HNE-4 in 100% of the rats in the E+ group. Further experiments are required to confirm or reject the preliminary data suggesting that changes in anxiety or HNE-4 level could also be biomarkers of post-traumatic epileptogenesis.  Funding: This study was supported by research grants R01NS033310 and R01NS065877 from the National Institutes of Health.