Inherent Susceptibility to Acquired Epilepsy in Selectively-Bred Rats Influences the Acute Response to Traumatic Brain Injury.

Traumatic brain injury (TBI) often causes seizures associated with a neuroinflammatory response and neurodegeneration. TBI responses may be influenced by differences between individuals at a genetic level, yet this concept remains understudied. Here, we asked whether inherent differences in one's vulnerability to acquired epilepsy would determine acute physiological and neuroinflammatory responses acutely after experimental TBI, by comparing selectively-bred 'seizure-prone' (FAST) rats versus 'seizure-resistant' (SLOW) rats, as well as control parental strains (Long Evans and Wistar rats). 11-week-old male rats received a moderate-to-severe lateral fluid percussion injury or sham-surgery. Rats were assessed for acute injury indicators and neuromotor performance, and bloods were serially collected. At 7-days post-injury, brains were collected for quantification of tissue atrophy by cresyl violet histology, and immunofluorescent staining of activated inflammatory cells. FAST rats showed an exacerbated physiological response acutely post-injury, with a 100% seizure rate and mortality within 24 h. Conversely, SLOW rats showed no acute seizures and a more rapid neuromotor recovery compared to controls. Brains from SLOW rats also showed only modest immunoreactivity for microglia/macrophages and astrocytes in the injured hemisphere compared to controls. Further, group differences were apparent between the control strains, with greater neuromotor deficits observed in Long Evans rats compared to Wistars post-TBI. Brain-injured Long Evans rats also showed the most pronounced inflammatory response to TBI across multiple brain regions, while Wistar rats showed the greatest extent of regional brain atrophy. These findings indicate that differential genetic predisposition to develop acquired epilepsy (i.e. FAST vs SLOW rat strains) determines acute responses after experimental TBI. Differences in the neuropathological response to TBI between commonly-used control rat strains is also a novel finding, and an important consideration for future study design. Our results support further investigation into whether genetic predisposition to acute seizures predicts the chronic outcomes after TBI, including the development of post-traumatic epilepsy.