Neuronal injury and death following focal mild brain injury: The role of network excitability and seizure

Document Type : Original Article


1 Department of Neurosciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

2 Shefa Neuroscience Research Center, Khatamolanbia Hospital, Tehran , Iran

3 Department of Neurosurgery, Department of Neurology, and Epilepsy Research Center, Munster University, Germany

4 Razavi Neuroscience Center, Razavi Hospital, Mashhad, Iran

5 Quchan Higher Health Education Center, Mashhad University of Medical Sciences, Mashhad, Iran

6 Neuroscience Research Center , Shahid Beheshti University of Medical Sciences, Tehran, Iran

7 Faculty of Pharmacy, Department of Toxicology, Tehran University of Medical Sciences, Tehran, Iran


Objective(s): While traumatic brain injury (TBI) is a predisposing factor for development of post-traumatic epilepsy (PTE), the occurrence of seizures following brain trauma can infuriate adverse consequences of brain injury. However, the effect of seizures in epileptogenesis after mild TBI cannot yet be accurately confirmed. This study was designed to investigate the histopathological and molecular modifications induced by seizures on traumatized brain.
Materials and Methods: Using a new method, head was traumatized and seizures were evoked by sub-convulsive dose of pentylenetetrazole (PTZ) fifteen days after induction of focal mild TBI. Convulsion assessments were performed one hour after PTZ injection and was followed by histopathological and molecular evaluations.
Results: A significantly higher score and longer duration of seizure attacks as well as higher number of epileptiform discharges were observed in the TBI+PTZ group compared to sham and TBI groups. An elevated number of apoptotic cells was observed in the TBI+PTZ group compared to sham and TBI rats. Molecular investigations revealed higher levels of Bax/Bcl2 ratio, Caspase 3, and NF-κB in the TBI+PTZ group compared to the other animal groups. The value of Nrf2 did not change after mild TBI compared to sham and PTZ control groups. Occurrence of seizures after TBI, however, significantly decreased the level of Nrf2.
Conclusion: Our data indicated that seizure occurrence following mild TBI aggravates cell injury and death via activation of neuroinflammatory processes and may increase the risk of PTE. Additionally, our results suggest a potential protective role of Nrf2 after chemically evoked PTE.


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