TABLE 1

Summarized PTE models with in vivo recordings of neuronal hyperexcitability

ModelSpecies/ PreparationSeizure SusceptibilityEEG RecordingAnimals with Epilepsy (%)Latency to SRSSeizure FrequencySeizure DurationEpileptiform Spiking, Discharges, HFOsReference
Parasagittal FPI
Rat: Sprague Dawley, young male; 3.75–4 atmN/A14 wks continuous recording beginning 2 wks postinjuryProbability of 92% epilepsy2–4 weeksN/AN/AN/AD'Ambrosio et al., 2004
Rat: Sprague Dawley, young male; 3.75–4 atmN/A8 hr/rat/week for 30 wks beginning 2 wks postinjuryProbability of 100% epilepsy3–5 weeks4.1 ±1 seizures/week4.2–11.8 sN/AD'Ambrosio et al., 2005
Rat; Sprague Dawley, young male; 1.8–2.2 atmIncreased susceptibility to PTZ-induced seizures at 12 wks postinjuryN/AN/AN/AN/AN/AN/AAtkins et al., 2010
Rat: Sprague Dawley, adult young male; 1.9–2.1 atmIncreased susceptibility to PTZ-induced seizures at 2 weeks postinjuryN/AN/AN/AN/AN/AN/ABao et al., 2011
Rat: Sprague Dawley, young male; 2.0 or 3.4 atmN/AUp to 17 weeks continuous recording, beginning 2 wks postinjuryProbability of 100% epilepsy2–18 weeks0.6 –3.0/hr1–144 sN/ACuria et al., 2011
Rat: Sprague Dawley, young male; 3.4–3.7 atmN/A1–2 24 hr recordings/rat/week for up to 2.5 months postinjuryN/A2–5 weeks0.25–1.75 seizures/hr1 s–4.5 minN/AD'Ambrosio et al., 2013
Rat: Wistar, adult maleN/A2 wks continuous recording beginning 1wk postinjury30%N/A6.3 seizures in 2 wks52.9 s11.5 discharges in 2 wksShultz et al., 2013
Rat: Sprague Dawley, adult male; 2.0 or 3.4 atmN/AUp to 12 months continuous recording, beginning 2 wks postinjury0%N/AN/AN/ASpike/wave discharges observed in both sham and injured rats. No epileptiform discharges/spikes observed in injured or sham rats.Rodgers et al., 2015
Rat: Sprague Dawley, young male; 1.8 atmN/ARandom increments of 12 hrs on/12 hrs off for 1–14 wks postinjury25%4–7 weeks2.83 seizures/weekMean = 47.5 sInterictal spikes observed in 58.3% of ratsNemes et al., 2016
Lateral FPI
Rat: Sprague Dawley, adult male; 0.5–1.2 atm, 1.5–1.6 atm, or 2.0–2.2 atmIncreased granule cell hyperexcitability at 1 wk postinjuryN/AN/AN/AN/AN/AN/ALowenstein et al., 1992
Rat: Sprague Dawley, adult male; 2.0 atmIncreased inhibition in dentate gyrus at 15 days postinjuryN/AN/AN/AN/AN/AN/AReeves et al., 1997
Rat: Sprague Dawley, adult male; 2.6–3.3 atmIncreased susceptibility to PTZ-induced seizures at 12 months postinjury4–7 wks continuous recording intervals for up to 12 months postinjury46%4–11 weeks0.3 seizures/dayMean = 137 ± 57 sInterictal spikes observed in epileptic ratsKharatishvili et al., 2006
Rat: Sprague Dawley, adult male; 2.3–3.2 atmIncreased susceptibility to PTZ-induced seizures at 12 months postinjury3 wks continuous recording at 11 months postinjury0%N/AN/AN/AIsolated spiking observed in 80% of TBI ratsKharatishvili et al., 2007
Rat: Wistar, P21; 2.0–2.2 atmIncreased susceptibility to kainate-induced seizures at 6 wks postinjuryN/AN/AN/AN/AN/AN/AEchegoyen et al., 2009
Rat: Sprague Dawley, P21 male; 2.2 atmNo change in PTZ susceptibility at 20 wks postinjuryBehavioral observation0%N/AN/AN/AN/AGurkoff et al., 2009
Rat: Sprague Dawley, adult male; 1.8–2.2 atmIncreased susceptibility to PTZ-induced seizures at 12 wks post-TBIN/AN/AN/AN/AN/AN/AAtkins et al., 2010
Rat: Sprague Dawley, adult male; 2.2 atmNo change in fluorothyl-induced seizures at 3 and 6 wks postinjuryN/AN/AN/AN/AN/AN/ASchwartzkroin et al., 2010
Mouse: C57BL/6S, adult male; 2.8–3.0 atmIncreased susceptibility to PTZ-induced seizures at 6 months postinjuryThree 2-wk continuous recordings at 6 m and 9 m post-TBI3% (1/30)N/A1 total seizure recorded during observation period91 sObserved epileptiform spiking in 71% injured miceBolkvadze and Pitkänen, 2012
Rat: Long-Evans, adult male; 2.2–2.4 atmN/AContinuous recording for 12 wks at 3 months postinjury100%N/A151 ±44 seizures/hr10–60 sN/AGoodrich et al., 2013
Mouse: C57BL/6S, adult male; 1.5–1.7 atmIncreased susceptibility to PTZ-induced seizures at 1month postinjuryN/AN/AN/AN/AN/AN/AMukherjee et al., 2013
Rat: Wistar, adult male; 3.2–3.5 atmN/A2 wks continuous recording at 1 wk postinjury30%N/AMean = 6.3 seizures/rat over 2 wksMean = 52.9 sObserved epileptic discharges in 22% of injured ratsShultz et al., 2013
Rat: Sprague Dawley, adult male; 2.4–2.8 atmN/AUp to 50 total hrs of continuous recording per rat at 5–33 wks post-TBI94% (16/17) incidence of nonconvulsive and 20% (1/5) convulsive seizuresN/A7/hrs nonconvulsive seizures; 0.05/hr convulsive seizures78–110 sN/ACampbell et al., 2014
Rat: Sprague Dawley, adult male; 3.2–3.5 atmN/AContinuous recording up to 26 weeks post-TBI, divided into early, intermediate, and late recording groups50% at 1 year follow-upN/AN/A14–30 sHFOs observed in 71% epileptic ratsReid et al., 2016
Rat: Sprague Sawley, adult male; 2.8–3.3 atmIncreased susceptibility to PTZ-induced seizures at 6 wks postinjuryN/AN/AN/AN/AN/AN/AWang et al., 2016b
Rat: Sprague Dawley, adult male; 2.8–3.3 atmN/AIntermittent recording of 24 hrs every 2 wks, up to 12 months postinjury55%2 weeks–10 monthsMean = 6 seizures/ratN/AN/AWang et al., 2016d
Rat: Sprague Dawley, young adult; mild: 1.2–1.5 atm, moderate: 1.8–2.2 atm, severe: 2.4–3.0 atmN/A1 year after injury, rats were recorded in 1 hr ECoG incrementsN/AN/AN/AN/AGreater spike/wave discharges observed in TBI ratsSick et al., 2017
Rat: Wistar, adult male; 2.8–3.2 atmIncreased susceptibility to PTZ-induced seizures at 46 days post-TBIIntermittent recordings of 48 hrs every wk at 2–5 wks post-TBI62.50%N/AMean = 7.8 seizures/ratN/AHigher frequency and power of spike-wave discharges and spiking observed in TBI versus sham ratsSmith et al., 2018
Central FPI
Rat: Sprague Dawley, adult male; 2.1 atm + PTZ kindlingSham and injured rats developed an equivalent convulsant response to PTZ.N/AN/AN/AN/AN/AN/AHamm et al., 1995
CCI
Rat: Sprague Dawley, P17; 2.0 mm depthNo change in threshold for tonic hind limb extension or minimal clonic seizures at P34–40; reduced threshold for minimal clonic seizures at P60–63N/AN/AN/AN/AN/AN/AStatler et al., 2008
Mouse: CD-1, adult; 0.5 or 1.0 mm depthN/ARandom 1–2 hr intervals of recording, up to 18 hrs total per mouse, beginning 42 days post-TBI20% (0.5 mm); 36% (1.0 mm)N/AN/AN/AN/AHunt et al., 2009
Rat: Sprague Dawley, P17; 2.0 mm depthN/AContinuous recording in 2-8 wk epochs for up to 3 months, beginning 4–8 months post-TBI13% (1/8)N/AN/A45-60 sObserved EEG spiking in 87.5% injured ratsStatler et al., 2009
Mouse: CD-1, adult; 1.0 mm depthN/ARandom 1–2 hr intervals totaling 4–6hr/wks up to 10 wks post-TBI40%6.5 ±1.3 weeksN/AN/AN/AHunt et al., 2010
Mouse: C57BL/6S, adult male; 0.5 mm depthIncreased susceptibility to PTZ-induced seizures at 6 months postinjuryThree 2-wk continous recordings at 6m and 9m postTBI9%N/A0.25/day50 ±14 sObserved epileptiform spiking in 81% injured miceBolkvadze and Pitkänen, 2012
Mouse: CD-1, adult male; 2.0 mm depthN/AContinuous recording for 16 wks post-TBI50% of untreated TBI mice82.3 10.2 days0.55 ±0.16 seizures/day35.5 ±2.8 sInterictal spike discharges were seen in some TBI miceGuo et al., 2013
Mouse: Plau deficient on C57BL/6J background, adult male; 0.5 mm depthBoth wild-type and Plau mice demonstrated increased susceptibiity to PTZ-induced seizures compared with shams2 wks continuous recording at 6 or 8 months post-TBI0% of wild-type or Plau miceN/AN/AN/AN/ABolkvadze et al., 2015
Mouse: CD-1, adult male; 1.0 mm depthN/ARandom 1–2hr intervals totaling 6hrs/wk at 6–10 wks post-TBI40%N/AN/A>30 sN/AButler et al., 2015
Rat: Sprague Dawley, adult male; 2.8 mm depthN/AWeek-long recordings up to 619 days post-TBI in some rats20%N/AN/A32 ±3 s (nonconvulsive); 91 ±12 (convulsive)N/AKelly et al., 2015
Mouse: PlauR deficient on C57BL6/J background, adult male; 0.5 mm depthSham and injured mice developed an equivalent convulsant response to PTZ2 wks continuous recording at 12 wks post-TBI14% (1/6) wild-type miceN/A1 observed seizure in 2 wks33 sN/ABolkvadze et al., 2016
Rat: Wistar, adult male; 2.0 mm depth + PTZ kindlingAccelerated PTZ kindling compared with shamN/AN/AN/AN/AN/AN/AEslami et al., 2016
Mouse: APP/PS1 on C57BL/6 background, adult male; 0.5 mm depthN/A 2 wks continuous recording at 6 or 14 wks post-TBI11% wild-type TBI mice; 88% APP/PS TBI miceN/A0.47/day35 sN/AMiszczuk et al., 2016
Mouse: C57BL/6, adult male; 1.0 mm depthIncreased firing of LV pyramidal cells within 1-2 mm of lesion core at 14 days post-TBIN/AN/AN/AN/AN/AN/APing and Jin, 2016b
Mouse: C57BL/6, adult male; 1.0 mm depthIncreased susceptibility to PTZ-induced seizures at 3 days postinjuryRandom 30 min recordings at 0, 3, or 24 hrs after TBI74% mice experienced immediate post-traumatic seizures<24 hrN/AN/AN/AWang et al., 2017
Mouse: C57BL/6S, adult male; 0.5 mm depthIncreased susceptibility to PTZ-induced seizures at 14 wks postinjury2 wks continuous recording at 10 wks postinjury10%N/AN/AN/AN/APijet et al., 2018
Rat: Sprague Dawley, adult male; 2.5–3.0 mm depthN/AUndefined intermittent recording parameters, up to 17 months post-TBI20.3%N/AN/AN/AN/ASun et al., 2018
Mouse: CD1, adult male; 1.0 mm depthN/A1 wk continuous recording at 7, 14, 30, 60, or 90 days post-TBI27.80%N/A0.43–0.71 seizures/dayN/AN/ASzu et al., 2020
Mouse: C57BL/6, adult male; 1.0 or 2.0 mm depthN/AContinuous recording for up to 4 months post-TBI, starting 10 days post-TBI33% (1.0 mm); 87% (2.0 mm)19.5 ±3 days (1.0 mm); 52.9 ±8 days (2.0 mm)0–2.74 seizures/day (1.0 mm); 0–4.17 seizures/day (2.0 mm)10–90 sEpileptiform discharges observed in 42% (1.0 mm) and 87% (2.0 mm) TBI miceGolub and Reddy, 2022
Weight Drop
Rat: Sprague Dawley, adult male; 20 g weight at 20 cmIncreased susceptibility to PTZ-induced seizures at 15 days or 7 weeksN/AN/AN/AN/AN/AN/AGolarai et al., 2001
Adult CD1 mice, male: closed skull injury + electroconvulsive shock 1 wk post-TBIIncreased susceptibility to PTZ-induced seizures at 15 days or 7 weeksN/AN/AN/AN/AN/AN/AChrzaszcz et al., 2010
Rat: Sprague Dawley, adult male; 50g weight at 60cm + PTZ administration on days 7 and 21 post-TBIAnimals subjected to both TBI and PTZ showed higher sensitivity to PTZ-induced seizures than noninjured PTZ-only rats1.5 hr recordings on days 7 and 21 post-TBI during PTZ testingN/AN/AN/AN/AN/AEfendioglu et al., 2020
Mouse: C57BL/6, adult; 100 g weight at 50 cmN/AContinuous recording up to 107 days post-TBI, starting 4 days post-TBI50%>3 weeks1–11 seizures/mouse during observation period12–15 sN/AShandra and Robel, 2020
Mouse: C57BL/6, adult male; closed skull, 50g weight at 80cmIncreased susceptibility to pilocarpine-induced seizures and status epilepticusN/A; observational scoringN/AN/AN/AN/AN/ABen Shimon et al., 2020
Penetrating and Blast Injury
Rat: Sprague Dawley, adult; 0.48, 0.63, or 0.7 cm balloon diameterN/A72 hrs continuous recording at time of injury and 2 hrs recording on days 7 and 14 post-TBI13% (mild); 39% (moderate); 59% (severe)Immediate seizures; N/A3.8 ±0.8 seizures/rat in 72 hrs (moderate); 10.5 ±2.6 seizures/rat in 72 hrs (severe)31.4 ±9.6 s (moderate); 33.6 ±5.0 s (severe)Epileptiform discharges observed in 30% (moderate) and 65% (severe) TBI animalsLu et al., 2011
Rat: Sprague Dawley, adult male; 0.63 cm balloon diameterN/A72 hrs continuous recording at time of injury71% immediate seizuresImmediate seizures; N/A9.5 ±2.5 seizures/rat in 72 hrs34.5 ±4 sN/AMountney et al., 2013
Rat: Sprague Dawley, adult male; hippocampal lesion with either copper or stainless steel wire insertionN/ARandom 2-wk continuous recording intervals for up to 11 months postinjury, beginning 6 wks postinjury96% copper; 15% stainless steelN/A3/day copper; 0.2/day stainless steel33.8 ±2.6 s copper; 25.7 ±0.7 s stainless steelN/AKendirli et al., 2014
Mouse: C57BL/6, adult male; peak overpressure of 14.6 psi, up to 3 blastsN/A72 hrs continuous recording at 2 days post-TBI, and intermittent 48–72 hr recordings at monthly intervals for up to 10 months0% (single blast); 33% (double); 50% (triple)N/A2.2 ±0.4 seizures/mouse (double) and 15 ±6.6 seizures/mouse (triple) during observation period39 ±4 s (>30 days post-TBI)N/ABugay et al., 2020
Cortical Undercut
Cat: adult both sexes; 3–4 mm depth and 13–15 mm distanceN/ANot described40%2–3 hrs after undercutN/A5–50 sObserved interictal spikes, sharp waves, spike-wave, and polyspike-wave complexes in 60% of animalsTopolnik et al., 2003a; 2003b
Cat: adult both sexes; 3–4 mm depth and 13–15 mm distanceN/AIntermittent weekly recording under anesthesia92%N/AN/AN/ALow-frequency spike-waves and polyspike-wave complexes observed intermingled with fast 10–20 Hz runs in all injured catsNita et al., 2006
Mouse - C57BL/6, adult male; 1.2 mm depth and 1-2 mm distanceIncreased susceptibility to PTZ-induced seizures at 15 days post-TBIContinuous recording for 50 or 90 days post-TBI50%17-34 days0.17 ± 0.17 seizures/day8-18 sEpileptic spikes observed in 71.4% of micePing and Jin, 2016a
  • ECoG = Electrocorticography.