Abstracts

Rationale: Human studies suggest younger age at time of traumatic brain injury (TBI) is a risk factor for early post-traumatic seizures while older age may be a risk factor for post-traumatic epilepsy (PTE). We used lateral fluid percussion injury (LFPI) in rats to determine whether age at injury has an effect on the development of PTE or other electrical kindling-related measures of brain excitability and seizure susceptibility.Methods: Male rats underwent moderate-severe LFPI or sham injury at post-natal day 19 or as an adult. Recording and stimulating electrodes were implanted two months later. Baseline EEG was recorded for one week to detect spontaneous seizures. Rats with LFPI were then divided to TBI/PTE- or TBI/PTE+ groups. After-discharge threshold and duration (ADT and ADD) were determined in response to callosal stimulation, then rats underwent 20 daily sessions of kindling. We studied kindling progression and the occurrence of secondary ADs (SAD), thought to originate from the hippocampus. Statistical analyses were performed on raw data to compare within Pup (P) or Adult (A) groups, and on data normalized to their respective Sham group to make comparisons across age.Results: Rats were divided into groups based on time of injury and baseline EEG: P/Sham; P/TBI/PTE-; P/TBI/PTE+; A/Sham; A/TBI/PTE-; and A/TBI/PTE+. Injury severity was not different in any TBI group (Table 1). P/TBI/PTE+ and A/TBI/PTE+ both had seizures originating from perilesional neocortex, but A/TBI/PTE+ had more frequent, longer duration seizures. Both P and A TBI/PTE+ had lower ADTs and longer ADDs versus their respective Shams and TBI/PTE- (Table 1). Normalized ADTs and ADDs were not different between PTE+ groups (Fig 1A, B). The number of stage 4/5 seizures during kindling was lower in PTBI/PTE+ versus P/Shams and P/TBI/PTE-, while A/TBI/PTE+ had more stage 4/5 seizures than A/Shams and P/TBI/PTE- (Table 1, Fig 1C). There were no differences between P groups in the latency to initial SAD, although A/TBI/PTE+ had a shorter latency to initial SAD than A/Shams and P/TBI/PTE+ (Table 1, Fig 1D).Conclusions: Some long term effects of LFPI on seizures and epilepsy are age-related, and appear to be linked to the development of PTE itself, not just TBI. LFPI at P19 or in adults caused PTE in the same proportion of rats, but seizures were more frequent and longer duration when injury occurred in adults. Injury at either age was associated with lower ADTs and longer ADDs, but the severity and progression of kindling-induced seizures increased in A/TBI/PTE+ and decreased in P/TBI/PTE+, suggesting younger brains have a greater capacity to withstand trauma-induced alterations that support PTE. The effect of LFPI on SADs only after adult injury suggests there may be hippocampal involvement with LFPI at an older age, supporting previous findings that the developing hippocampus is not as susceptible to injury. Future studies of the brain after LFPI may help lead to further understanding of the epileptogenic process occurring after TBI at different ages, and whether different interventions may be needed to prevent PTE in children versus adults.