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. 2019 May 13;8(5):448. doi: 10.3390/cells8050448

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© 2019 by the authors.

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

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Sex-dependent developmental changes in neonatal seizure susceptibility and responses to antiseizure medications (ASMs) summarized from two neonatal seizure models [52,53]. (counter-clockwise) (A) During development males had a higher neonatal seizure susceptibility at P7 than P10 (P7 HIE Males vs. P10 HIE Males: One-way ANOVA; F_5,59 = 19.44, p = 0.0044). In contrast, females did not have significant differences in age-dependent seizure susceptibility from P7 to P10. Males and females, both had significantly higher P7 seizure burdens when neonatal seizures were induced with chemoconvulsants (PTZ) when compared to unilateral carotid ligation (HIE)-induced seizures (P7 HIE Males vs. P7 PTZ Males: One-way ANOVA; F_5,59 = 19.44, p = 0.0004; P7 Females vs. P7 PTZ Females: F_5,59 = 19.44, p < 0.0001). (B) PTZ induced neonatal seizures at P7 were responsive to phenobarbital (PB) at 1 h after the initial PTZ injection. Bumetanide (BTN) administration at 2h resulted in significant seizure aggravation in females (P7 PB Females vs. P7 BTN Females: Two-way ANOVA; F_2,22 = 14.6, p < 0.001). Aggravation of seizures by bumetanide was dependent upon sex as females had significantly greater seizure aggravation than males (P7 BTN Females vs. P7 BTN Males: Two-way ANOVA; F_2,22 = 43.97, p < 0.001). (C) HIE induced seizures were non-responsive to PB in contrast to the PTZ induced seizures at P7. Neither PB nor BTN administration significantly suppressed HIE seizures in either sex. (D) HIE induced seizures at P10 are responsive to PB, with BTN administration significantly aggravating seizures in females (Two-way ANOVA; F_2,18 = 2.334, p = 0.007). ** signifies p < 0.01; *** signifies p < 0.001.