Levetiracetam Reduces High Frequency Oscillations but Not Early Seizures in Rats Following Lateral Fluid Percussion Injury: Einstein Data. an epibios4rx Project 2 Study
Abstract number :
1.029
Submission category :
1. Basic Mechanisms / 1C. Electrophysiology/High frequency oscillations
Year :
2022
Submission ID :
2204312
Source :
www.aesnet.org
Presentation date :
12/3/2022 12:00:00 PM
Published date :
Nov 22, 2022, 05:24 AM
Authors :
Aristea Galanopoulou, MD PhD – Albert EInstein College of Medicine; Patricia Saletti, PhD – Albert EInstein College of Medicine; Jack Lin, N/A – Albert Einstein College of Medicine; Florencia Chena-Becerra, PhD – Albert Einstein College of Medicine; Christos Panagiotis Lisgaras, PhD – Albert Einstein College of Medicine; Wenzhu Mowrey, PhD – Albert Einstein College of Medicine; Wei Liu, N/A – Albert Einstein College of Medicine; Qianyun Li, N/A – Albert EInstein College of Medicine; Pablo Casillas-Espinosa, PhD – Monash University; Matt Hudson, PhD – Monash University; Idrish Ali, PhD – Monash University; Nigel Jones, PhD – Monash University; Sandy Shultz, PhD – Monash University; Cesar Santana-Gomez, PhD – UCLA; Terence O'Brien, MD PhD – Monash University; Richard Staba, PhD – UCLA; Solomon Moshé, MD – Albert EInstein College of Medicine
Rationale: Severe traumatic brain injury (TBI) causes early seizures and high frequency oscillations (HFOs). Pathological HFOs have been proposed as candidate biomarkers of post-TBI epileptogenesis. Prophylactic use of levetiracetam is commonly used during the first week after severe TBI. The EpiBioS4Rx Project 2 multicenter study (Einstein, Monash, UCLA) investigates the effects of prophylactic levetiracetam during the first post-TBI week upon seizures, HFOs and plasma biomarkers, in rats exposed to lateral fluid percussion injury (LFPI). Here we present the Einstein data.
Methods: Adult male Sprague-Dawley rats (11 weeks old) underwent a left parietal 5 mm craniotomy; only LFPI rats, but not sham (n=4), received a ~3.2 atm pressure pulse. LEV200 rats (n=21) received LEV at 200 mg/kg bolus injection ip after the hit, followed by 200 mg/kg/day via a subcutaneous (SC) minipump, which was placed an hour later and for 7 days. LEV0 rats (n=20) underwent the same procedures, but received saline instead. Electrodes (bilateral screw frontal, central and occipital; bipolar perilesional cortical and hippocampal microelectrodes, ground, reference) were implanted 1hr post-craniotomy. Video-electroencephalography (vEEG) was recorded continuously for 14 days. Twenty minute epochs from days 0, 6, and 13 were scored for HFOs using bandpass filtering between 80-200Hz (ripples, R) and 200-500Hz (fast ripples, FR) and the RippleLab detector. Statistics included Fisher’s exact test or linear mixed model analyses with repeated measures.
Results: LEV had no significant effect on incidence of early seizures: LEV0: 50% (10/20 rats); LEV200: 38% (8/21 rats) (p=0.54, Fisher’s exact test). On day 0, LEV0 LFPI rats had higher incidence of HFOs (R=72.7%; FR=90.9%; R+FR=100%) compared to LEV200 LFPI (R=33.3%; FR=50%, p=0.045; R+FR=50%, p=0.014) or sham (R=50%; FR=25%, p=0.03; R+FR=50%, p=0.057). No group differences in HFO incidence were seen on day 6 or 13. LEV200 also reduced the HFO hourly rates on day 0 compared to LEV0 for R or R+FR (p< 0.05), but the effect did not persist on days 6 and 13. There was no significant difference in HFO incidence between LFPI rats with or without early seizures.
Basic Mechanisms