Factors influencing the acute pentylenetetrazole‐induced seizure paradigm and a literature 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,, 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.

Pre-existing Toxoplasma gondii infection increases susceptibility to pentylenetetrazol-induced seizures independent of traumatic brain injury in mice

“…Interestingly, female mice took less time to develop a generalized convulsive seizure and had a higher seizure severity when compared to males, contrary to previous reports that found no difference between sexes ( Yuskaitis et al, 2021 ). This may be due to the use of different strains, age and physiologic stressors between studies.…”

“…This may be explained by differences in the age at time of injury (i.e., pediatric compared to adult) as pediatric populations respond differently to TBI, have a higher incidence of PTE, and are more likely to develop post-traumatic seizures compared to older groups ( Hwang et al, 2019 ; Webster et al, 2019 ; Elsamadicy et al, 2021 ; Mariajoseph et al, 2022 ). It may also be explained by differences in strain and methodologies used, as murine strains present diverse responses to PTZ, responses can vary between injury models, lower PTZ dosage can result in a greater proportion of subconvulsive events, epileptogenic sequelae vary with the stage of recovery being assessed, and physiologic stressors including EEG implantation and single-housing can increase the number of PTZ-induced seizures ( Bolkvadze and Pitkänen, 2012 ; Mukherjee et al, 2013 ; Smith et al, 2018 ; Yuskaitis et al, 2021 ). Furthermore, although no effect of TBI on response to PTZ was evident at this timepoint, it is possible that the CCI was still pro-epileptogenic in terms of the development of spontaneous seizures.…”

The effects of crude alkaloid extract of Matricaria chamomilla L. on convulsions induced by pentylenetetrazole in chicks

“…This study was concerned with the effect of crude alkaloids extract of MC on the behavior alteration and the level of brain neurotransmitters GABA and glutamate in chicks PTZ-induced convulsions. PTZ is often used to induce the development and study of convulsions, as well as, it is used to evaluate the potential efficacy of antiepileptic substances in experimental animals (23). The results of the study showed that the treatment of chicks by PTZ exhibited obvious convulsive behaviors.…”

DEPDC5-dependent mTORC1 signaling mechanisms are critical for the anti-seizure effects of acute fasting

“…injected with 65 mg/kg PTZ during the light phase of the light-dark cycle. Mice were monitored by an investigator blinded to genotype and treatment for generalized tonic-clonic seizures over a 20-min period, as previously described (Yuskaitis et al, 2021). After the 20-min observation period, mice were sacrificed.…”

“…We first tested if 24-h fasting protects mice from seizures using an acute PTZ-induced seizure paradigm (Figure 1A) (Yuskaitis et al, 2021). Fasting for 24 h significantly reduced PTZ-induced seizures from 56% having seizures in the fed state to 22% in fasted mice (Figure 1B).…”