Objective: To investigate the alterations in hippocampal neurons,nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3) inflammasome,microglia,and myelin in rats with post-traumatic stress disorder(PTSD). Methods: A PTSD rat model was established using the single prolonged stress(SPS) paradigm.Anxiety and cognitive functions were evaluated through the open field test,elevated plus maze,and Morris water maze.Histopathological changes in hippocampal neurons were assessed using hematoxylin and eosin(HE)staining.The expression levels of NLRP3 and iba-1(a microglial marker) in the hippocampus were examined using immunofluorescence staining.Immunohistochemical staining and Luxol Fast Blue staining were performed to investigate alterations in hippocampal myelin. Results: Hippocampal neurons in PTSD rats exhibited damage,with increased activation of the NLRP3 inflammasome and microglia,and elevated myelin content. Conclusion The pathogenesis of PTSD may be associated with hippocampal neuronal damage,inflammatory responses,and changes in myelin.