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Epilepsy phenotype and its reproducibility after lateral fluid percussion-induced traumatic brain injury in rats: Multicenter EpiBioS4Rx study project 1.
Ndode-Ekane, Xavier Ekolle; Ali, Idrish; Santana-Gomez, Cesar; Andrade, Pedro; Immonen, Riikka; Casillas-Espinosa, Pablo; Paananen, Tomi; Manninen, Eppu; Puhakka, Noora; Smith, Gregory; Brady, Rhys D; Silva, Juliana; Braine, Emma; Hudson, Matt; Yamakawa, Glen R; Jones, Nigel C; Shultz, Sandy R; Harris, Neil; Wright, David K; Gröhn, Olli; Staba, Richard; O'Brien, Terence J; Pitkänen, Asla.
Affiliation
  • Ndode-Ekane XE; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Ali I; Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.
  • Santana-Gomez C; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
  • Andrade P; Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA.
  • Immonen R; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Casillas-Espinosa P; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Paananen T; Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.
  • Manninen E; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
  • Puhakka N; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Smith G; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Brady RD; A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland.
  • Silva J; Department of Neurosurgery, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, USA.
  • Braine E; Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.
  • Hudson M; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
  • Yamakawa GR; Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.
  • Jones NC; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
  • Shultz SR; Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.
  • Harris N; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
  • Wright DK; Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.
  • Gröhn O; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
  • Staba R; Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.
  • O'Brien TJ; Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Parkville, Victoria, Australia.
  • Pitkänen A; Department of Neurology, Alfred Health, Melbourne, Victoria, Australia.
Epilepsia ; 65(2): 511-526, 2024 Feb.
Article in En | MEDLINE | ID: mdl-38052475
ABSTRACT

OBJECTIVE:

This study was undertaken to assess reproducibility of the epilepsy outcome and phenotype in a lateral fluid percussion model of posttraumatic epilepsy (PTE) across three study sites.

METHODS:

A total of 525 adult male Sprague Dawley rats were randomized to lateral fluid percussion-induced brain injury (FPI) or sham operation. Of these, 264 were assigned to magnetic resonance imaging (MRI cohort, 43 sham, 221 traumatic brain injury [TBI]) and 261 to electrophysiological follow-up (EEG cohort, 41 sham, 220 TBI). A major effort was made to harmonize the rats, materials, equipment, procedures, and monitoring systems. On the 7th post-TBI month, rats were video-EEG monitored for epilepsy diagnosis.

RESULTS:

A total of 245 rats were video-EEG phenotyped for epilepsy on the 7th postinjury month (121 in MRI cohort, 124 in EEG cohort). In the whole cohort (n = 245), the prevalence of PTE in rats with TBI was 22%, being 27% in the MRI and 18% in the EEG cohort (p > .05). Prevalence of PTE did not differ between the three study sites (p > .05). The average seizure frequency was .317 ± .725 seizures/day at University of Eastern Finland (UEF; Finland), .085 ± .067 at Monash University (Monash; Australia), and .299 ± .266 at University of California, Los Angeles (UCLA; USA; p < .01 as compared to Monash). The average seizure duration did not differ between UEF (104 ± 48 s), Monash (90 ± 33 s), and UCLA (105 ± 473 s; p > .05). Of the 219 seizures, 53% occurred as part of a seizure cluster (≥3 seizures/24 h; p >.05 between the study sites). Of the 209 seizures, 56% occurred during lights-on period and 44% during lights-off period (p > .05 between the study sites).

SIGNIFICANCE:

The PTE phenotype induced by lateral FPI is reproducible in a multicenter design. Our study supports the feasibility of performing preclinical multicenter trials in PTE to increase statistical power and experimental rigor to produce clinically translatable data to combat epileptogenesis after TBI.
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Full text: 1 Database: MEDLINE Main subject: Epilepsy, Post-Traumatic / Epilepsy / Brain Injuries, Traumatic Limits: Animals Language: En Year: 2024 Type: Article
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Full text: 1 Database: MEDLINE Main subject: Epilepsy, Post-Traumatic / Epilepsy / Brain Injuries, Traumatic Limits: Animals Language: En Year: 2024 Type: Article