title: Traumatic Brain Injury Causes a Tacrolimus-Sensitive Increase in Non-Convulsive Seizures in a Rat Model of Post-Traumatic Epilepsy.
abstract: Epilepsy is a significant but potentially preventable complication of traumatic brain injury (TBI). Previous research in animal models of acquired epilepsy has implicated the calcium-sensitive phosphatase, calcineurin. In addition, our lab recently found that calcineurin activity in the rat hippocampus increases acutely after lateral TBI. Here we use a calcineurin inhibitor test whether an acute increase in calcineurin activity is necessary for the development of late post-traumatic seizures. Adult rats were administered the calcineurin inhibitor Tacrolimus (5mg/kg; i.p.) 1 hour after lateral fluid percussion TBI and then monitored by video-electrocorticography (video-ECoG) for spontaneous seizure activity 5 weeks or 33 weeks later. At 5 weeks post-TBI, we observed epileptiform activity on the video-ECoG of brain injured rats but no seizures. By 33 weeks post-TBI though, nearly all injured rats exhibited spontaneous seizures, including convulsive seizures which were infrequent but lasted minutes (18% of injured rats), and non-convulsive seizures which were frequent but lasted tens of seconds (94% of injured rats). We also identified non-convulsive seizures in a smaller subset of control and sham TBI rats (56%), reminiscent of idiopathic seizures described in other rats strains. Non-convulsive seizures in the brain injured rats, however, were four-times more frequent and two-times longer lasting than in their uninjured littermates. Interestingly, rats administered Tacrolimus acutely after TBI showed significantly fewer non-convulsive seizures than untreated rats, but a similar degree of cortical atrophy. The data thus indicate that administration of Tacrolimus acutely after TBI suppressed non-convulsive seizures months later.
authors.affiliation: Anatomy and Neurobiology, Virginia Common Wealth University, Richmond, VA.
authors.forename: John N
authors.initials: JN
authors.lastname: Campbell
authors.affiliation: Neurology, Virginia Commonwealth University, Richmond, VA.
authors.forename: Anandh
authors.initials: A
authors.lastname: Gandhi
authors.affiliation: Physiology and Biophysics, Virginia Common Wealth University, Richmond, VA.
authors.forename: Baljinderjit
authors.initials: B
authors.lastname: Singh
authors.affiliation: Pharmacology and Toxicology, Virginia Common Wealth University, Richmond, VA.
authors.forename: Severn B
authors.initials: SB
authors.lastname: Churn
keywords: Absence seizure; EEG; Epileptogenesis; FK-506; Post-traumatic epilepsy; Tonic-clonic seizure