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. 2021 Nov 22;48:102197. doi: 10.1016/j.redox.2021.102197

Fig. 7.

Fig. 7

Effects of endogenous adropin on infarct volume and long-term neurobehavioral outcomes in aged mice subjected to pMCAO. A, Timeline of behavioral testing and magnetic resonance imaging (MRI) scanning in aged (18–24 months) male mice subjected to pMCAO. B-E, Representative T2-weighted MRI scans and 3-dimensional (3D) reconstruction images of the ischemic lesion in adropin knockouts (Enho−/−), adropin overexpressing mice (AdrTg) and their corresponding wild-type littermates at 14 days after pMCAO (B, D, Left: T2-MRI for Enho+/+ vs. Enho−/−, WT vs. AdrTg; Right: 3D-image for Enho+/+ vs. Enho−/−, WT vs. AdrTg). The ischemic area was marked with a discontinuous red line in T2 maps and depicted as a dark red area in the left hemisphere in 3D images. Graphical data show that deficiency of the Enho gene resulted in a significant increase in brain infarct volume compared to Enho+/+ controls (C). In contrast, transgenic overexpression of adropin resulted in a smaller brain infarction than WT littermates (E). Unpaired t-test, *P < 0.05, **P < 0.01. Enho+/+ (n = 8), Enho−/− (n = 11), WT (n = 9), AdrTg (n = 11). F–P, Neurobehavioral tests were performed before (baseline) and defined days (48h, 7d, and 14d) after pMCAO as depicted in panel A. Sensorimotor and recognition memory functions were evaluated by adhesive removal test (F, G, H, I) and novel object recognition (L–P). Deficiency of the Enho gene significantly increased the time mice took to sense and remove the sticker on the affected paw at days 7 and 14 after stroke compared to Enho+/+ mice (F, G). In contrast, AdrTg mice took significantly less time to sense and remove the sticker on the affected paw at day 7 than the corresponding WT littermates (H, I). Graphical representation, tracking maps, and corresponding heat maps of time spent per location in the open field chamber show that Enho−/− mice have a worse recovery in long-term recognition memory performance at 14d after pMCAO compared to the Enho+/+ mice (M, O). Still, AdrTg mice show much better cognitive function recovery than the WT littermates (N, P). There is no significant difference in body weight loss between Enho+/+ and Enho−/− mice over 14 days after stroke (J). Bodyweight loss was significantly attenuated after 48 h following pMCAO in the AdrTg mice compared to the WT littermates (K). Two-way ANOVA with Bonferroni post-tests, *P < 0.05, **P < 0.01, ***P < 0.001. Enho+/+ (n = 8), Enho−/− (n = 11), WT (n = 9), AdrTg (n = 12). (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)