Figure 10.

NMDA receptor antagonists prevent seizure-induced medullary SD, respiratory suppression and fatal outcome in Cacna1a^S218L mice. Cacna1a^S218L mice received acute intraperitoneal treatment with vehicle (VEH), MK-801 (1 mg/kg), or memantine (MEM; 10 mg/kg) 30 min before an IC stimulation-induced seizure. A, Proportion of seizures with fatal or nonfatal outcome, with or without SD in the VLM. Note that all fatal seizures were associated with VLM SD. Animals pretreated with MK-801 or MEM had seizures that were significantly less likely fatal (*p < 0.05, χ² test) and less likely associated with VLM SD (##p < 0.001, χ² test). B, Mean respiratory rate (RR) during the last minute of seizure behavior, indicating respiratory suppression during seizures with VLM SD (red and black). RR was significantly greater for animals pretreated with MK-801 or MEM (**p < 0.0001, ANOVA with Dunnett's test). C, Seizures were significantly shorter for animals pretreated with MK-801 or MEM (**p = 0.001 and *p = 0.013, respectively, ANOVA with Dunnett's test). When excluding hindlimb clonus (gray), MK-801 pretreatment resulted in shorter seizures, whereas MEM did not (#p = 0.045 and p = 0.755, respectively, ANOVA with Dunnett's test). Hindlimb clonus only occurred for seizures associated with VLM SD (VEH: n = 15; MEM: n = 1).