Fig. 2.
Treatment with synthetic adropin peptide reduces infarct volume and improves long-term neurological deficits in mice subjected to pMCAO. A, Timeline of experimental procedure in adult (10–12 weeks) mice subjected to pMCAO. B, Representative Cresyl violet-stained coronal sections from vehicle- and adropin-treated mice at 21 days after pMCAO. C, Post-ischemic treatment with synthetic adropin34-76 peptide (900 nmol/kg; i.v.) at the onset of pMCAO significantly reduces brain infarct volume. Unpaired t-test, ***P < 0.001, n = 9–10 per group. D-L, Neurobehavioral tests were performed on vehicle- and adropin-treated mice before (baseline) and on defined days (24h, 48h, 7d, 14d, and 21d) after pMCAO as depicted in panel A. Sensorimotor function was evaluated by the adhesive removal test (D, E), cylinder test (F, G), open field test (H–J) and corner test (K, L). Recording data show that treatment with 900 nmol/kg of synthetic adropin peptide significantly reduces the time for mice to sense and remove the sticker on the affected paw (D, E). Also, mice treated with synthetic adropin show sustained recovery on impaired sensorimotor function, as shown by a dramatic increase in the percentage of first contact events with both forelimbs compared to the vehicle group (G). Graphical representation and representative tracking maps with corresponding heat maps of time spent per location in the open field chamber show that adropin-treated mice recovered better in total distance traveled at 48h after pMCAO than vehicle animals (I, J). In the corner test, a significant improvement on left turns (ipsilateral side) was observed at 48h post-stroke in mice treated with adropin compared to vehicle (L). M, There was no significant difference in body weight loss between adropin- and vehicle-treated mice over 21 days after pMCAO. Two-way ANOVA with Bonferroni post-tests, *P < 0.05, **P < 0.01, ***P < 0.001. Vehicle (n = 10), Adropin (n = 9). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)