Pathologic electrographic changes after experimental traumatic brain injury

Anatol Bragin; Lin Li; Joyel Almajano; Catalina Alvarado-Rojas; Aylin Y Reid; Richard J Staba; Jerome Engel Jr

doi:10.1111/epi.13359

Pathologic electrographic changes after experimental traumatic brain injury

Epilepsia. 2016 May;57(5):735-45. doi: 10.1111/epi.13359. Epub 2016 Mar 25.

Authors

Anatol Bragin^{1

2}, Lin Li¹, Joyel Almajano¹, Catalina Alvarado-Rojas¹, Aylin Y Reid¹, Richard J Staba¹, Jerome Engel Jr^{1

2

3

4}

Affiliations

¹ Department of Neurology, University of California Los Angeles, Los Angeles, California, U.S.A.
² Brain Research Institute, University of California Los Angeles, Los Angeles, California, U.S.A.
³ Department of Neurobiology, University of California Los Angeles, Los Angeles, California, U.S.A.
⁴ Department of Psychiatry and Biobehavioral Medicine, University of California Los Angeles, Los Angeles, California, U.S.A.

Abstract

Objective: To investigate possible electroencephalography (EEG) correlates of epileptogenesis after traumatic brain injury (TBI) using the fluid percussion model.

Methods: Experiments were conducted on adult 2- to 4-month-old male Sprague-Dawley rats. Two groups of animals were studied: (1) the TBI group with depth and screw electrodes implanted immediately after the fluid percussion injury (FPI) procedure, and (2) a naive age-matched control group with the same electrode implantation montage. Pairs of tungsten microelectrodes (50 μm outer diameter) and screw electrodes were implanted in neocortex inside the TBI core, areas adjacent to TBI, and remote areas. EEG activity, recorded on the day of FPI, and continuously for 2 weeks, was analyzed for possible electrographic biomarkers of epileptogenesis. Video-EEG monitoring was also performed continuously in the TBI group to capture electrographic and behavioral seizures until the caps came off (28-189 days), and for 1 week, at 2, 3, and 6 months of age, in the control group.

Results: Pathologic high-frequency oscillations (pHFOs) with a central frequency between 100 and 600 Hz, were recorded from microelectrodes, beginning during the first two post-FPI weeks, in 7 of 12 animals in the TBI group (58%) and never in the controls. pHFOs only occurred in cortical areas within or adjacent to the TBI core. These were associated with synchronous multiunit discharges and popSpikes, duration 15-40 msec. Repetitive pHFOs and EEG spikes (rHFOSs) formed paroxysmal activity, with a unique arcuate pattern, in the frequency band 10-16 Hz in the same areas as isolated pHFOs, and these events were also recorded by screw electrodes. Although loss of caps prevented long-term recordings from all rats, pHFOs and rHFOSs occurred during the first 2 weeks in all four animals that later developed seizures, and none of the rats without these events developed late seizures.

Significance: pHFOs, similar to those associated with epileptogenesis in the status rat model of epilepsy, may also reflect epileptogenesis after FPI. rHFOSs could be noninvasive biomarkers of epileptogenesis.

Keywords: Electroencephalography; Epileptogenesis; Pathologic high frequency oscillations; Repetitive HFOs and spikes; Seizure; Spindles; Traumatic brain injury.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Analysis of Variance
Animals
Brain Injuries, Traumatic / complications*
Brain Injuries, Traumatic / etiology
Brain Waves / physiology
Disease Models, Animal
Electrodes, Implanted
Electroencephalography*
Epilepsy, Post-Traumatic / etiology*
Epilepsy, Post-Traumatic / pathology*
Male
Neocortex / physiopathology*
Percussion / adverse effects
Rats
Rats, Sprague-Dawley

Abstract

Publication types

MeSH terms

Grants and funding