Fig. 4

Fndc5/irisin mediates the neurorestorative effects of LIPUS on experimental VaD. A Experimental outline. Knockdown the expression of hippocampal Fndc5 using shRNA before 7days of BCAS. Transcranial LIPUS was applied 24 h after BCAS and subsequently daily with a stimulation time of 5 min at an ultrasound pressure of 0.51 MPa for a period of 28 days. B, C Fndc5 mRNA expression and irisin concentration in hippocampus of adult mice were respectively detected using qPCR and ELISA on day 28 after BCAS. D Hippocampal synaptic plasticity was analyzed using Patch Clamp, average traces of fEPSP in hippocampal slices collected on day 28 after BCAS. E The data of fEPSP at 120 min. F, G Hippocampal TGF-β and IL-10 were determined using ELISA on day 28 after BCAS. H Exploratory time on old or new object in novel object recognition test were illustrated in histogram. I The errors in radial arm water maze test were continuously measured in each block on day 28 after BCAS. J The data of errors in last block were counted in a histogram. K Global Fndc5 knock-out mice (F5KO) was employed to mechanism exploration, contextual fear test was used to assess cognitive deficit on day 28 after BCAS. the percentage of freezing time obtained on day 28 after BCAS were illustrated in histogram. Sham, sham-operated mice; BCAS, mice were subjected to BCAS injury; LIPUS, BCAS adult mice with LIPUS treatment; shFndc5 or shLuc, LIPUS-treated adult BCAS mice with intrahippocampal injection with lentiviral particles expressing shRNA against murine Fndc5 or luciferase. (n = 8 per group. All data are expressed as mean ± SEM, *P < 0.05, **P < 0.01, ***P < 0.001, ns means no statistical significance)