Citation

Lu XM, Browning J, Liao Z, Cao Y, Yang W, Shear DA. J. Neurotrauma 2019; ePub(ePub): ePub.

Affiliation

Walter Reed Army Institute of Research, 8394, Brain Trauma Neuroprotection, Silver Spring, Maryland, United States; deborah.a.shear.civ@mail.mil.

Copyright

(Copyright © 2019, Mary Ann Liebert Publishers)

DOI

10.1089/neu.2019.6573

PMID

31530242

Abstract

Traumatic brain injury (TBI) carries a risk of developing post-traumatic epilepsy (PTE). Currently animal models that replicate clinical PTE (delayed spontaneous and recurrent seizures) are limited, which hinders preclinical research. In this study, we used two rat models of penetrating ballistic-like brain injury (PBBI) and closed-head injury (CHI) to induce spontaneous seizures and also measure changes in seizure susceptibility. In the PBBI model, two trajectories (frontal and lateral) and two injury severities for each trajectory were evaluated. In the CHI model, a single projectile impact to the dorsal/lateral region of the head was tested. Continuous video-EEG recordings were collected for 10 days at 1 or 6 month(s) post injury. After EEG recording, all rats were given a sub-convulsant dose of pentylenetetrazole (PTZ) to challenge the seizure susceptibility. The video-EEG recording did not detect PTE following the PBBI. Only one CHI rat demonstrated persistent and recurrent non-convulsive seizures detected at 6 months post-injury. However, after PTZ challenge, 50-100% of the animals across different TBI groups experienced seizures. Seizure susceptibility increased over time from 1 to 6 months post-injury across the majority of TBI groups. However, the injury severity effects were not apparent within the PBBI model, but evident between PBBI and CHI models. These results demonstrated the difficulties in detecting delayed spontaneous post-traumatic seizures even in a high risk model of penetrating brain injury. However, the PTZ-induced increase in seizure susceptibility indicated the existence of vulnerable risk of epileptogenesis following TBI, which may be considered as an alternative research tool for preclinical studies of PTE.

Language: en

Keywords

EEG; EPILEPSY; HEAD TRAUMA; Penetrating Ballistic-like Brain Injury; Rat