Aim of the study. Determining the role of surgical stress in the formation of p53-positive and dark neurons (DN) in the hippocampus; analyzing their parallel formation in the pyramid hippocampus layer. Material and methods. Septoplasty was modeled in 20 mature Wistar male rats. Histological hippocampus slices were analyzed, where the number of DN and p53-positive neurons was determined on Days 2, 4, and 6 after the surgery. Results. Compared to the control group (5 animals), the number of DN and p53-positive neurons in experimental animals increased in all periods. A direct relation between the increased number of DN and p53-positive neurons was confirmed. Conclusion. Septoplasty modeling in rats leads to the activation of pathological cascades, which in turn changes the multifunctional properties of neurons in the pyramidal hippocampus layer and promotes their neuroplasticity. The activation of neuronal NMDS-re-ceptors during stress possibly initiates two pathways of neuronal life — the onset of p53 protein expression and the formation of DN. Both pathways may finally lead to apoptosis. The formation of DN and the p53 protein expression in them are most likely related and may possibly provide the neuroprotective mechanisms. © 2023, Media Sphera Publishing Group. All rights reserved.