Figure 1
Inhibition of IRAP reduced infarct volume and improved post-stroke motor and neurological function. Treatment with either 0.1 or 1 nmol HFI419 or, 1 nmol SJM164 at 2, 24, 48 and 70 h post-stroke significantly reduced (A) striatal, (B) cortical and (C) total infarct. Delaying first treatment of 1 nmol HFI419 to 6 h post-stroke, followed by treatment at 24, 48 and 70 h post-stroke reduced (B) cortical and total (C) infarct volume (n = 7–10, *P < 0.05, **P < 0.01, ***P < 0.001 vs. vehicle; the data represented as mean ± SEM and analysed by one-way ANOVA followed by a Dunnett’s test or unpaired t-test). (D) Neurological deficits were significantly improved following treatment with an IRAP inhibitor beginning at 2 or 6 h post-stroke, where a higher score indicates greater neurological deficit (pre = pre-stroke, 24 = 24 h post-stroke, 70 = 70 h post-stroke; n = 7–14, #P < 0.05, ##P < 0.01, P < 0.0001 vs time-matched sham, *P < 0.05, ***P < 0.001, ****P < 0.0001 vs. time-matched vehicle; data was analysed with a two-way repeated-measures ANOVA followed by a Tukey’s test; n = 5–11). Motor function was significantly improved following treatment with an IRAP inhibitor. (E) Treatment with 1 nmol HFI419 beginning at 6, 24, 48 and 70 h post-stroke significantly improved performance on the rotarod compared to vehicle treatment (n = 6–10, *P < 0.05, ***P < 0.001, analysed by one-way ANOVA followed by a Dunnett’s test). (F) IRAP inhibition beginning at 2 or 6 h post stroke, reduced the percentage of foot faults while traversing the ledge-beam test at 24 and 70 h post-stroke (n = 7–11, #P < 0.05, ##P < 0.01, P < 0.0001 vs time-matched sham, *P < 0.05, ***P < 0.001, ****P < 0.0001 vs. time-matched vehicle; analysed with a two-way repeated-measures ANOVA followed by a Tukey’s test). All data is represented as mean ± SEM.
