Epileptic seizures are caused by abnormal activity in the brain.Due to its complex etiology, it is difficult to predict the seizure occurrence.Previously, we found the abnormal swimming patterns in traumatic brain injury (TBI) zebrafish are highly similar to the pentylenetetrazol (PTZ)-induced seizure phenotypes.Moreover,expression profile of epilepsy markers, c-fos and gabrg2, are significantly altered in TBI zebrafish as well.Thus, we hypothesize TBI zebrafish may serve as disease model to resolve the etiological mechanism of post-traumatic seizures (PTS).Using a 27G needle punch approach, we inflicted traumatic injury in adult zebrafish cerebellum.We first monitored the behavioral phenotypes of TBI zebrafish and surveyed the expression of known epileptic markers, c-fos and gabrg2, in the damaged brain tissue.We found 35% of TBI zebrafish showed positive signs of epileptic seizures, and the symptoms could be relieved by valproic acid (VPA), which is a FDA approved anticonvulsant for treating epileptic seizures.Next, we identified genes associated with PTS by microarray transcript profiling between TBI and PTZ-treated zebrafish.We found atf3 and c-jun were significantly up-regulated in both conditions, suggesting their roles in chemical-induced and post-traumatic epileptogenesis.Subsequent analysis revealed TBI could sensitize PTZ-induced seizures via up-regulation of the Atf3 and C-jun signaling pathways, further implying their upstream activator could regulate post-traumatic epileptogenesis.In conclusion,our PTS zebrafish model is a useful tool to study post-traumatic epileptic seizures and for anticonvulsant drug screen.Our findings may help to develop early diagnosis assay to predict the occurrence of post-traumatic seizures.