TY - JOUR
T1 - Factors influencing the acute pentylenetetrazole-induced seizure paradigm and a literature review
AU - Yuskaitis, Christopher J.
AU - Rossitto, Leigh Ana
AU - Groff, Karenna J.
AU - Dhamne, Sameer C.
AU - Zhang, Bo
AU - Lalani, Lahin K.
AU - Singh, Achint K.
AU - Rotenberg, Alexander
AU - Sahin, Mustafa
N1 - Funding Information:
This study was also supported by the BCH Neurodevelopmental Behavioral Core of the Intellectual and Developmental Disabilities Research Center (NIH U54HD090255), the BCH Rosamund Stone Zander Translational Neuroscience Center, and the BCH Experimental Neurophysiology Core. C.Y. receives grant support from NIH 1K08NS107637, the Hearst Foundation, and Boston Children’s Office of Faculty Development Career Development Fellowship.
Funding Information:
This study was also supported by the BCH Neurodevelopmental Behavioral Core of the Intellectual and Developmental Disabilities Research Center (NIH U54HD090255), the BCH Rosamund Stone Zander Translational Neuroscience Center, and the BCH Experimental Neurophysiology Core. C.Y. receives grant support from NIH 1K08NS107637, the Hearst Foundation, and Boston Children?s Office of Faculty Development Career Development Fellowship. This study was also supported by the BCH Neurodevelopmental Behavioral Core of the Intellectual and Developmental Disabilities Research Center (NIH U54?HD090255), the BCH Rosamund Stone Zander Translational Neuroscience Center, and the BCH Experimental Neurophysiology Core. C.Y. receives grant support from NIH 1K08NS107637, the Hearst Foundation, and Boston Children?s Office of Faculty Development Career Development Fellowship. We thank all of the members of the Rotenberg and Sahin labs.
Funding Information:
This study was also supported by the BCH Neurodevelopmental Behavioral Core of the Intellectual and Developmental Disabilities Research Center (NIH U54 HD090255), the BCH Rosamund Stone Zander Translational Neuroscience Center, and the BCH Experimental Neurophysiology Core. C.Y. receives grant support from NIH 1K08NS107637, the Hearst Foundation, and Boston Children’s Office of Faculty Development Career Development Fellowship. We thank all of the members of the Rotenberg and Sahin labs.
Funding Information:
M.S. reports grant support from Novartis, Roche, Pfizer, Biogen, Ipsen, LAM Therapeutics, Astellas, Bridgebio and Quadrant Biosciences. He has served on Scientific Advisory Boards for Sage, Roche, Celgene, Aeovian, Regenxbio and Takeda. None of the other authors has any conflict of interest to disclose.
Publisher Copyright:
© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
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U2 - 10.1002/acn3.51375
DO - 10.1002/acn3.51375
M3 - Article
C2 - 34102033
AN - SCOPUS:85107580051
SN - 2328-9503
VL - 8
SP - 1388
EP - 1397
JO - Annals of Clinical and Translational Neurology
JF - Annals of Clinical and Translational Neurology
IS - 7
ER -