Inhibition of ASIC1a Improves Behavioral Recovery after Stroke

Protective effect of ASIC1a knock-out on infarct volume after MCAO. a, Twenty-four hours after 30 min MCAO, mice were killed, and infarct volumes were determined using TTC staining. b, Knock-out of ASIC1a significantly reduced brain infarct volume. Data are presented as mean ± SEM and analyzed by t test (n = 4–5 for each group). *p < 0.05 when compared with ASIC1a^+/+.

Knock-out of ASIC1a accelerates neurological deficit recovery. Neurological scoring was done prior to MCAO for baseline measurement and at the specified timepoints post-MCAO. Both ASIC1a^+/+ and ASIC1a^−/− mice had significant focal deficits over a 28 d period following MCAO. a, The focal deficit of ASIC1a^−/− mice significantly improved from day 1 deficit a week earlier than ASIC1a^+/+ mice. b, ASIC1a^−/− mice had general deficits for fewer days and significantly improved from day 1 deficit 14 d earlier than ASIC1a^+/+ mice. Data are presented as mean ± SEM and analyzed by two-way ANOVA (n = 11–13 for each group). The asterisks represent the significant differences as compared with day 0 measurement. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. The pound signs represent the significant differences as compared with day 1 measurement. ^#p < 0.05, ^##p < 0.01, ^###p < 0.001, ^####p < 0.0001.

Knock-out of ASIC1a improved mobility recovery but not sidedness bias after stroke. a, Representative visualization of the open field test. b, Both ASIC1a^+/+ and ASIC1a^−/− mice had reduced mobility after MCAO. Only ASIC1a^−/− mice significantly recovered mobility. c, Both ASIC1a^+/+ and ASIC1a^−/− mice had significantly right-sidedness bias after MCAO and neither group significantly recovered within 28 d. Data are presented as mean ± SEM and analyzed by two-way ANOVA (open field n = 13–18 for each group, corner n = 7–11 for each group). The asterisks represent the significant differences as compared with baseline measurement. *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. The pound signs represent the significant differences as compared with first day of measurement after MCAO. ^#p < 0.05, ^##p < 0.01, ^###p < 0.001, ^####p < 0.0001.

Protective effect of ASIC1a inhibition on infarct volume after focal cerebral ischemia. a, Representative images of TTC stained brains 24 h after 30 min MCAO. b, PcTX1-treated mice had a significantly reduced infarct volume when compared with vehicle mice. Data are presented as mean ± SEM and analyzed by t test (n = 5 for each group). *p < 0.05 when compared with vehicle.

Acute inhibition of ASIC1a improves neurological deficit recovery. Neurological scoring was done prior to MCAO for baseline measurement and at the specified timepoints post-MCAO using the previously described stroke scale. a, PcTX1 mice have significantly increased focal deficits for the first 3 d, and vehicle mice had significantly increased deficits for 7 d post-MCAO. b, PcTX1 mice had significantly increased general sickness on days 1, 3, and 5 post-MCAO and significantly recovered from that increase on day 21 post-MCAO. Vehicle mice had significantly increased general sickness on all days up to 7 d post-MCAO and significantly recovered from that increase on day 21 post-MCAO. Data are presented as mean ± SEM and analyzed by two-way ANOVA (n = 9–11 for each group). The asterisks represent the significant differences as compared with baseline measurement *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001. The pound signs represent the significant differences as compared with day 1 measurement ^#p < 0.05, ^##p < 0.01, ^###p < 0.001, ^####p < 0.0001. The crosses represent the significant differences as compared with day 5 measurement ⁺p < 0.05, ⁺⁺p < 0.01, ⁺⁺⁺p < 0.001, ⁺⁺⁺⁺p < 0.0001.