TLR4 and Cognitive impairment: In the aging, increased neuroinflammation induced by TLR4 would be associated with neurotrophic loss changes [45], and the increase level of BDNF, NGF in TLR4-KO group of our study would alleviate neuroinflammation [46] and apoptosis [47, 48] in the hippocampus which can ameliorate the reduced neuronal growth and neuronal survival by increasing the protection from damage [49] and result in the reduced cognitive impairment [18].