Fig. 5: Preventive administration of WS-3, the TRPM8 agonist, reduced the elevation of extracellular glutamate levels, beta-band power, and seizure severity in WT mice after the seizure inducer injection; however, WS-3 did not decrease in TRPM8-KO mice.

A Average heart rate in each group. Transitions in (B) glutamate levels and (C) beta-band power were averaged every 5 min. B, C Gray columns indicated each evaluation time zone (B; pre-PG: 35–40 min, post-PG: 55–60 min and C; pre-PG: 35–40 min, post-PG: 95–100 min). D Glutamate levels in each gray column in B: 5 min before and 15–20 min after the seizure inducer injection. E Beta-band power 5 min before the seizure-inducer injection and during the last 5-min period. F Maximum seizure score during the 60 min after the end of inhalation anesthesia. Correlation between (G) peak glutamate levels and beta-band power (R² = 0.754), H peak glutamate levels and maximum seizure score (ρ = 0.905), and (I) logarithmic value of beta-band power during the last 5 min of anesthesia and the maximum seizure score (ρ = 0.908). Opened black or blue circles and green or orange triangles indicate (B, C) mean or (F–I) raw data in each group. Data in (A–F) are presented as the mean ± SEM, n = 5 WT mice and n = 4 TRPM8-KO mice. *p < 0.05, **p < 0.01, and ***p < 0.001, Tukey’s test. ^†p < 0.05 and ^†††p < 0.001, paired t-test. ^‡p < 0.05, Steel-Dwass test after Kruskal-Wallis test. DMSO, dimethyl sulfoxide; EDs, epileptiform discharges; PG, penicillin G potassium; TRPM8, transient receptor potential melastatin 8; TRPM8-KO, TRPM8 homozygous knockout; WT, wild-type.