Figure 1. Systemic inhibition of aromatase after seizure onset suppresses electrographic seizures in gonadectomized rats.

(A) Schematic of experimental design. (B, C) Representative EEG (B) and normalized power spectrum (C) from one vehicle (Veh, top)- and one fadrozole (Fad, bottom)-treated rat. For EEG, the 1^st seizure in each animal is shown on the left. Teal bars above heatmaps indicate seizures detected by 5x baseline power in the β-low γ (10–50 Hz) range as the threshold. (D) Mean ± SEM normalized EEG amplitude plotted in 5 min bins for vehicle (blue, n=12)- and fadrozole (orange, n=9)-treated rats. The escalation of seizures evident in vehicle-treated rats during the 2^nd hr of testing was inhibited by fadrozole. (E) Mean ± SEM percent time in seizure using 5x baseline thresholds of EEG amplitude showing that the progressive increase in time in seizure evident in vehicle-treated rats was also inhibited by fadrozole. (F) Mean ± SEM normalized power spectrogram plotted in 1 Hz bins for δ-θ (1–10 Hz), β-low γ (10–50 Hz), and ripple (100–200 Hz) frequency ranges for vehicle (blue) and fadrozole (orange) rats showing the KA-induced increase in power relative to baseline for each frequency range examined. Increases in δ-θ (p<0.001, ANOVA) and β-low γ (p=0.01, ANOVA) power were lower in fadrozole- than vehicle-treated rats. (G) Mean ± SEM normalized EEG β-low γ power plotted in 5 min bins for vehicle (blue) and fadrozole (orange) rats showing the lack of seizure escalation in fadrozole-treated rats. (H) Mean ± SEM percent time in seizure plotted in 5 min bins using 5x baseline thresholds of β-low γ power for vehicle (blue) and fadrozole (orange) rats also showing the lack of seizure escalation in fadrozole-treated rats. *p<0.05 and **p<0.01 between vehicle- and fadrozole-treated rats, post-hoc unpaired t-tests. BL = baseline.

DOI: http://dx.doi.org/10.7554/eLife.12917.003

Figure 1—figure supplement 1. No difference in characteristics of the 1^st seizure in animals subsequently treated with vehicle or fadrozole.

(A-D) Representative raw EEG traces (top) and corresponding changes in β-low γ power (bottom) are shown for female (A, C) and male (B, D) rats subsequently treated with vehicle (A, B) or fadrozole (C, D). Increased β-low γ (10–50 Hz) power was evident for each 1^st seizure. (E–I) There were no significant group differences between rats that subsequently received vehicle or fadrozole in (E) latency to seizure onset, (F) seizure duration, (G) amplitude, (H) β-low γ power, or (I) time to i.v. injection (i.e., the time between KA injection and the start of 2 hr testing). P values were >0.25 for all parameters, unpaired t-tests.

DOI: http://dx.doi.org/10.7554/eLife.12917.004

Figure 1—figure supplement 2. Comparison of manual and 3x, 5x, and 10x baseline thresholds.

(A) Raw EEG, (B) normalized EEG amplitude, and (C) normalized β-low γ (10–50 Hz) power from a representative vehicle-treated rat. The colored bars above the traces indicate seizures detected manually (A), or using 3x, 5x, or 10x baseline threshold (B, C), as indicated on the right. While there were differences in sensitivity to minor seizures (e.g., 1^st seizure at ~200 s) and the ability to resolve seizures during the merging phase (4000–7200 s), the effects of systemic fadrozole to suppress seizures were detected with all thresholds tested. (D, E) Systemic administration of fadrozole attenuated seizure progression, so that the fadrozole-treated rats spent significantly less time in seizure during the 2^nd hr of testing, whether seizures were detected based on an increase in EEG amplitude (3x: F_1,19=15.93, p<0.01; 10x: F_1,19=5.79, p<0.05, D) or an increase in β-low γ power (3x: F_1,19=20.97, p<0.001; 10x: F_1,19=12.62, p<0.01, E) and regardless of the threshold used. *p<0.05 and **p<0.01 for the 2^nd hr between vehicle- and fadrozole-treated rats, post-hoc unpaired t-tests. Statistics for 5x baseline threshold data are reported in the Results.

DOI: http://dx.doi.org/10.7554/eLife.12917.005