Fig. 1.

Stroke decreases endogenous adropin levels in the brain and plasma, and treatment with synthetic adropin peptide reduces infarct volume in mice subjected to pMCAO. A, Western blot shows stroke-induced loss of endogenous adropin levels in the ipsilateral cerebral cortex in a time-dependent manner. B, Densitometric analysis shows that brain adropin levels are significantly reduced from 24 to 48 h after left middle cerebral artery occlusion. One-way ANOVA with Bonferroni post-tests, *P < 0.05, n = 3–4 per group. C, Plasma adropin level was reduced after stroke as assessed by a commercially available adropin ELISA kit. Unpaired t-test, P = 0.0604, n = 5–7 per group. D, Dynamic changes of synthetic adropin peptide in plasma. Plasma was collected before (pre-injection) and at 5 min, 1h, 4h, and 24h after one bolus injection with synthetic adropin^34-76 peptide (900 nmol/kg; i.v.). Levels of synthetic adropin peptide in plasma dropped to almost pre-injection values within 4 h. One-way ANOVA with Bonferroni post-tests, ***P < 0.001, n = 4 per group. E, Treatment timeline for adult mice subjected to permanent middle cerebral artery occlusion (MCAO) with different doses of synthetic adropin peptide. F, Representative 2,3,5-triphenyltetrazolium chloride (TTC)-stained coronal sections from vehicle-, 90-, 900- and 2700-nmol/kg adropin-treated mice. G, Treatment with synthetic adropin^34-76 peptide (90–2700 nmol/kg; i.v.) at the onset of pMCAO significantly reduces brain infarct volume in a dose-dependent manner. One-way ANOVA with Bonferroni post-tests, *P < 0.05, **P < 0.01, n = 7–9 per group. H, Analysis of cortical infarct area per-1mm slice shows that the decrease in cortical infarction by 900 nmol/kg adropin is seen throughout the cortex. Two-way ANOVA with Bonferroni post-tests, *P < 0.05, ***P < 0.001. Vehicle (n = 9), Adropin (n = 9). I, Timeline for adult mice subjected to pMCAO with 3h delayed synthetic adropin treatment. J, Representative TTC-stained coronal sections of vehicle- and adropin-treated mice. K, Treatment with synthetic adropin peptide (900 nmol/kg; i.v.) at 3h after pMCAO significantly reduces brain infarct volume. Unpaired t-test, ***P < 0.001, n = 6–8 per group. L, Analysis of cortical infarct area per-1mm slice shows a reduction in cortical infarction by adropin treatment at different levels of the cerebral cortex. Two-way ANOVA with Bonferroni post-tests, *P < 0.05, **P < 0.01, ***P < 0.001. Vehicle (n = 6), Adropin (n = 8).