Figure 2. A–D, Inhibition of hippocampus kindling epileptogenesis in PRKO mice. A, PRKO mice displayed marked retardation of kindling development as expressed by a lower mean seizure stage at the corresponding stimulation session. B, AD duration was markedly lower in PRKO than in WT mice. The single asterisks in A and B indicate that the mean value is significantly (p < 0.05) different from that in WT control. C, Rate of kindling development (number of stimulations for stage 5 seizures) was significantly inhibited in PRKO mice. Values represent the mean ± SEM (n = 7–10 mice per group). *p < 0.01 versus WT control. D, Sample traces of electrographic AD seizure activity in PRKO mice during hippocampus kindling development. The traces show depth recordings from a right hippocampus stimulating-recording electrode after 1st and 20th stimulations. The arrows at the bottom indicate kindling stimulation that was followed by an artifact or a period of blanking surrounding the 1 s stimulus. The slow negative wave after stimulation was digitally subtracted in each trace. Behavioral seizure stages are indicated on the trace. At the 20th stimulation, the WT mouse had a 37 s seizure discharge with 31 s generalized (stage 4/5) seizures, whereas the PRKO mouse had only a 17 s seizure discharge with 15 s partial (stage 2/3) seizures. E–H, Inhibition of hippocampus kindling epileptogenesis in WT mice treated with PR antisense oligos. E, Western blot analysis of PR expression in the hippocampus. Representative immunoblots of PR and β-actin in WT mice treated with PR missense or antisense oligonucleotides. Hippocampus tissues were isolated ∼20 h after intracerebroventricular infusion of 10 nmol of PR antisense or missense oligonucleotides in WT mice. F, WT mice treated with PR antisense oligos displayed a striking retardation of kindling development as expressed by a lower mean seizure stage at the corresponding stimulation session. G, AD duration was markedly lower in the PR antisense group. The single asterisks in F and G indicate that the mean value is significantly (p < 0.05) different from that in missense control. H, Rate of kindling development (number of stimulations for stage 5 seizures) was significantly inhibited in antisense-treated WT mice. Values represent the mean ± SEM (n = 7–10 mice per group). *p < 0.01 versus missense control. I–K, Comparison of the rate of hippocampus kindling epileptogenesis in three models of PR intervention: PRKO mouse model (I), PR antisense model (J), and the PR antagonist RU-486 model (K). Mean seizure stage values were fit to the linear function Sn = Rn + A, where Sn is the mean seizure stage for the nth stimulation, R is the rate of kindling, and A is set equal to zero in all three approaches. Values represent the mean ± SEM. *p < 0.05 versus control group.