In vitro experiments further showed that the microglial phenotype of MCAO-induced BV2 cells treated with TLR-4 inhibitor TAK-242 and NF-κB inhibitor BAY 11-7082 was similar to that of hesperidin, verifying that hesperetin is neuroprotective by inhibiting TLR4-NF-κB pathways, which provides new targets and strategies for neuroprotection and nerve repair after ischemic stroke. This evidence concerns the gene TLR4 and ischemic stroke.