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ObjectiveHypertension is a public health challenge worldwide due to its high prevalence and multiple complications. Hypertension-induced damage to the hippocampus leads to behavioral changes and various brain diseases. Despite the multifaceted effects of hypertension on the hippocampus, the mechanisms underlying hippocampal lesions are still unclear.MethodsThe 32-week-old spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats were selected as the study subjects. Behavioral experiments such as an open field test (OFT), an elevated plus maze (EPM) test, and the Morris water maze (MWM) test were performed to show the behavioral characteristics of the rats. A comprehensive transcriptomic and metabolomic analysis was performed to understand the changes in the hippocampus at the metabolic and genetic levels.ResultsBehavioral tests showed that, compared to WKY rats, SHR showed not only reduced memory capacity but more hyperactive and impulsive behavior. In addition, transcriptomic analysis screened for 103 differentially expressed genes. Metabolomic analysis screened 56 metabolites with significant differences, including various amino acids and their related metabolites.ConclusionComprehensive analysis showed that hypertension-induced hippocampal lesions are closely associated with differential metabolites and differential genes detected in this study. The results provide a basis for analyzing the mechanisms of hypertension-induced hippocampal damage.