Harmonization of pipeline for preclinical multicenter plasma protein and miRNA biomarker discovery in a rat model of post-traumatic epileptogenesis

Alaa Kamnaksh, Noora Puhakka, Idrish Ali, Gregory Smith, Roxanne Aniceto, Jesse McCullough, Shalini Das Gupta, Xavier Ekolle Ndode-Ekane, Rhys Brady, Pablo Casillas-Espinosa, Matt Hudson, Cesar Santana-Gomez, Riikka Immonen, Pedro Andrade de Abreu, Nigel Jones, Sandy Shultz, Richard J. Staba, Terence J. O'Brien, Denes Agoston, Asla Pitkänen

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The Epilepsy Bioinformatics Study for Antiepileptogenic Therapy (EpiBioS4Rx) is an international, multicenter, multidisciplinary study aimed at preventing epileptogenesis (EpiBioS4Rx: https://epibios.loni.usc.edu/). One of the study's major objectives is the discovery of diagnostic, prognostic, and predictive plasma protein and microRNA (miRNA) biomarkers that are sensitive, specific, and translatable to the human condition. Epilepsy due to structural brain abnormalities, secondary to neurological insults such as traumatic brain injury (TBI), currently represents ∼50% of all epilepsy cases. In the preclinical EpiBioS4Rx study, TBI was induced in adult male Sprague Dawley rats using a standardized protocol for lateral fluid-percussion injury. Whole blood was collected from the tail vein at baseline and 2, 9 and 30 days post-injury and processed for plasma separation. Biomaterial properties, sample preparation and integrity, and choice of analysis platform can significantly impact measured marker levels and, in turn, interpretation with respect to injury and/or other variables. We present here the results of procedural harmonization for the first 320 rats included in the EpiBioS4Rx study study, from three international research centers, and preliminary proteomic and miRNA analyses. We also discuss experimental considerations for establishing rigorous quality controls with the goal of harmonizing operating procedures across study sites, and delivering high-quality specimens for preclinical biomarker discovery in a rat model of post-traumatic epilepsy (PTE).

Original languageEnglish
Pages (from-to)92-101
Number of pages10
JournalEpilepsy Research
Publication statusPublished - 1 Jan 2019


  • Case report form
  • Common data elements
  • Post-traumatic epilepsy
  • Quality control
  • Standardization
  • Traumatic brain injury

Cite this

Kamnaksh, A., Puhakka, N., Ali, I., Smith, G., Aniceto, R., McCullough, J., Das Gupta, S., Ndode-Ekane, X. E., Brady, R., Casillas-Espinosa, P., Hudson, M., Santana-Gomez, C., Immonen, R., Abreu, P. A. D., Jones, N., Shultz, S., Staba, R. J., O'Brien, T. J., Agoston, D., & Pitkänen, A. (2019). Harmonization of pipeline for preclinical multicenter plasma protein and miRNA biomarker discovery in a rat model of post-traumatic epileptogenesis. Epilepsy Research, 149, 92-101. https://doi.org/10.1016/j.eplepsyres.2018.11.009