Figure 1. P7C3-S243 Preserves Memory after Blast-Mediated TBI.

(A) Daily IP administration of P7C3-S243 for 11 days in divided daily doses for the total amount indicated dose-dependently preserved memory in the Barnes maze probe test in blast-injured mice, as measured by the most stringent measure of percent time in escape area (5 cm radius around the escape hole). Treatment with an intermediate dose (3 mg/kg/d) of the active (−)-P7C3-S243 enantiomer preserved normal performance to the level displayed by sham-injured mice. By contrast, mice treated with the same dose of the less active (+)-P7C3-S243 enantiomer showed the same deficit as injured mice that were treated with vehicle. (B) Daily administration of P7C3-S243 was initiated at later time periods after injury to define the window of therapeutic efficacy. Whereas both 3 and 30 mg/kg/d doses preserved normal function when treatment was initiated 24 hours after injury, only the 30 mg/kg/d dose was efficacious when treatment was initiated at 36 hours. When treatment was initiated 48 hours after injury, no protective efficacy was noted at any dose. (C) Oral administration of the highly active (−)-P7C3-S243 enantiomer preserved normal hippocampal dependent memory at 3, 10 and 30 mg/kg/day doses. Every group shown consisted of 25 male C57/Bl6 mice, aged 12–14 weeks, and data was collected and scored in an automated manner blind to treatment group. Data are represented as mean ± SEM. Significance was determined by two way ANOVA with Bonferroni post-hoc analysis. p-value labeled as *<0.05, **<0.01, ***<0.001, and ****<0.0001 compared to blast-injured animals treated with vehicle. See also Figure S1 and S2.