Additionally, we offered explanation for preliminary mechanisms regarding the role of Fndc5/irisin in the LIPUS-induced protection against VaD using hippocampal primary cell cultures: LIPUS promotes hippocampal neurons to secrete irisin by increasing Fndc5 expression, those neuron-secreted irisin directly accelerate synaptic plasticity, and help LIPUS to drive astrocytes toward neuroprotective phenotype, then alleviating cognitive impairment. This evidence concerns the gene FNDC5 and Cognitive impairment.