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. 2018 Aug 10;8:11987. doi: 10.1038/s41598-018-30486-7

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Baseline and post-PB seizure burden, ictal events and durations at P7 and P10 (A) P7 seizures were PB-resistant. ANA12 given IP immediately after the carotid ligation reversed PB-resistance in a dose-dependent manner at P7. (B) At P7, number of ictal events were reduced significantly with PB and further with each graded dose of ANA12 + PB. (C) Ictal durations were not significantly modulated by any treatment. (D) At P10, seizures were PB-responsive. ANA12 improved PB-efficacy with each graded dose. (E) At P10, number of ictal events were reduced significantly with PB alone, and further reduced per graded increase in dose of ANA12 + PB at P10 that was significant only at 5 mg/kg dose. (F) Only 0.5 mg/kg on ANA12 significantly decreased ictal duration at P10. All comparisons done via two-way ANOVA; bars with “*” denote significance between 1^st and 2^nd hour within a treatment (*P < 0.05, **P < 0.01, ***P < 0.001). Bars with “#” denote significance between groups compared to PB (^#P < 0.05, ^##P < 0.01, ^###P < 0.001). Bars with “@” denote significance between groups compared to ANA 5 + PB (^@P < 0.05, ^@@P < 0.01, ^@@@P < 0.001).