We focused on the role of hippocampal neuronal death in CCH-induced cognitive impairment and possible interventions and found that the small molecular compound D3NB, which can cross the BBB, may target and regulate neurotrophic factors (such as the GDNF/GFRα1/Ret/AKT/ERK signaling factors) and reduce hippocampal neuronal apoptosis in CCH rats (Xiong et al., 2017; Li et al., 2019b). This evidence concerns the gene GFRA1 and Cognitive impairment.