Introduction: Approximately 10% of patients with traumatic brain injuries develop a late-onset seizure condition known as post-traumatic epilepsy, which often impedes recovery and worsens prognosis. The mechanisms underlying the onset of recurrent seizures in post-traumatic epilepsy are poorly understood. We propose that sustained activation of the JNK pathway may predispose the brain to further susceptibility to injury.
Methods: Experimental groups (n=5 animals/group) consisted of c57/bl6 mice receiving 1) a sub-convulsive dose of kainic acid (15 mg/kg i.p.), 2) a sub-convulsive dose of kainic acid administered 72 hours after a single TBI exposure of moderate intensity, and 3) a sub-convulsive dose of kainic acid administered 72 hours after a single TBI exposure of severe intensity. Control groups included mice receiving blast-induced TBI without kainic acid. Seizure activity was detected via a modified Racine scale from 1 to 72 hours after injury with or without kainic acid injection and by beam breaks at 72 hours. Gliosis and JNK activity were measured at 72 hours post-injury.
Results: Mice administered a sub-convulsive dose of kainic acid following a blast exposure had a 4 fold relative intensity increase in phosphorylated JNK 54 and 46 (p<0.001) and a significant increase in gliosis measured with GFAP (p<0.001) in the ipsilateral hippocampus and temporal cortex compared to controls. Mice exposed to kainic acid following a blast exposure had significant reduction in beam breaks at 72 hours compared to controls indicating seizure-like activity. This was confirmed with the modified Racine scale scoring where mice exposed to kainic acid following a blast exposure had significantly higher scores (3-4) compared to scores (1-2) in the blast only group.
Conclusions: JNK signaling may play an important role in post-traumatic epilepsy and the generation of glutamate excitotoxicity. Future experiments are warranted to investigate the role of JNK inhibitor as a treatment option for post-traumatic seizures.
Patient Care: Understanding how this pathway contributes to post-traumatic epilepsy may open new avenues for treatment.
Learning Objectives: JNK signaling may contribute to epileptic foci development after neurotrauma