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Background Baicalin has a significant anti-inflammation effect and is widely used in the clinical treatment of stroke.Most of the studies of Toll-like receptor 2/4 (TLR2/4) during cerebral ischemia had defined their specific expressions in microglia in hippocampus tissue.To explore the targets of baicalin in stroke,we detected the expressions of TLR2/4 in vitrolvivo.Methods By constructing a cerebral ischemia-reperfusion model in vivo and glucose oxygen deprivation model,we successfully induced neuron damage,then added baicalin and detected expressions of TLR2/4,nuclear factor-κB (NF-κB),tumor necrosis factor-alpha (TNFa),and interleukin-1β (IL-1β)in mRNA level and protein level.Results We found distinct upregulations of TLR2/4 and TNFα in both mRNA level and protein level in PC12 cells and primary neurons.Moreover,TLR2/4 and TNFα expressions were significantly higher in mice hippocampus treated with cerebral ischemia-reperfusion.Baicalin could downregulate the expressions of TLR2/4 and TNFα in the damaged cells and mice hippocampus effectively.Conclusions Neurons could respond to the damage and activate the related signal pathway directly.TLR2/4responsed to the damage and sent the signal to downstream factor TNFα through activating NF-κB.Baicalin could inhibit the inflammatory reaction in neuron damage and TLR might be its targets,which explained why baicalin could widely be used in the clinical treatment of stroke.