Figure 5. LDN/OSU-0212320 reduces mortality rate, chronic seizure, and neuronal death following pilocarpine-induced SE.

Mice received compound (i.p., 40 mg/kg) and were treated with pilocarpine 3 hours later. Mice that reached SE received compound daily, and chronic seizures were recorded 4 weeks after SE for a 2-week period (15 independent experiments in a total of 153 vehicle- and 152 compound-treated mice). (A) Acute seizure severity (maximal seizure activity of each animal within 2 hours after pilocarpine injection). The percentage of mice that reached each seizure stage did not differ between the two groups. (B) Latency (time interval between pilocarpine injection and the indicated stage). Latency did not differ between the two groups. (C) Mortality rate (percentage of mice that died in each experiment, n = 15). A significant decrease was observed in the compound-treated group on days 7 and 60 after SE. (D–F) Spontaneous recurrent seizures. (D) Percentage of mice (vehicle, n = 19; compound, n = 25) that developed <1, 1~2, 2~3, or >3 stage V seizures in an 8-hour period. (E) Average number of stage V seizures in an 8-hour period. (F) Frequency of stage V seizures during each day of recording. Chronic seizure frequency was significantly reduced in compound-treated mice. Arrows indicate that a mouse died on that day. (G and H) Hippocampal damage. Nine sets of brains 8 weeks after SE were analyzed with cresyl violet staining (15–20 sections/mouse). (G) Representative images of the dentate hilus. Scale bar: 20 μm. (H) Quantitative analysis of hilar cells. Compound treatment significantly attenuated cell damage. (I) A strong positive correlation was detected between hilar cell loss and chronic seizure frequency. *P < 0.05.