Factors influencing the acute pentylenetetrazole-induced seizure paradigm and a literature review

Christopher J. Yuskaitis, Leigh Ana Rossitto, Karenna J. Groff, Sameer C. Dhamne, Bo Zhang, Lahin K. Lalani, Achint K. Singh, Alexander Rotenberg, Mustafa Sahin

Research output: Contribution to journalArticlepeer-review

Abstract

Objective: To confirm the critical factors affecting seizure susceptibility in acute pentylenetetrazole (PTZ) mouse epilepsy models and evaluate the prior literature for these factors. Methods: Serial cohorts of wild-type mice administered intraperitoneal (IP)-PTZ were aggregated and analyzed by multivariate logistic regression for the effect of sex, age, background strain, dose, and physiologic stress (i.e., EEG implantation and/or single-housing) on seizure response. We assessed the reporting of these factors in a comprehensive literature review over the last 10 years (2010–2020). Results: We conducted aggregated analysis of pooled data of 307 mice (220 C57BL/6J mice and 87 mixed background mice; 202 males, 105 females) with median age of 10 weeks (range: 6–49 weeks) with acute PTZ injection (dose range 40–65 mg/kg). Significance in multivariate analysis was found between seizures and increased PTZ dose (odds ratio (OR) 1.149, 95% confidence interval (CI) 1.102–1.205), older age (OR 1.1, 95% CI 1.041–1.170), physiologic stress (OR 17.36, 95% CI 7.349–44.48), and mixed background strain (OR 0.4725, 95% CI 0.2315–0.9345). Literature review identified 97 papers using acute PTZ-seizure models. Age, housing, sex, and background were omitted by 61% (59/97), 51% (49/97), 18% (17/97), and 8% (8/97) papers, respectively. Only 17% of publications specified all four factors (16/97). Interpretation: Our analysis and literature review demonstrate a critical gap in standardization of acute PTZ-induced seizure paradigm in mice. We recommend that future studies specify and control for age, background strain, sex, and housing conditions of experimental animals.

Original languageEnglish (US)
Pages (from-to)1388-1397
Number of pages10
JournalAnnals of Clinical and Translational Neurology
Volume8
Issue number7
DOIs
StatePublished - Jul 2021
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology

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