NLRP3-Mediated Neuroinflammation Participates in Resilience to PSD in C57BL/6 Mice

Background: Post-stroke depression (PSD) is a common complication of stroke, in which neuroinflammation plays a crucial role. Depression resilience has garnered significant attention in recent years, yet its relevance to PSD remains unexplored. Methods: In this study, we assessed emotional behaviors in C57BL/6 mice subjected to stereotaxic injection of endothelin-1 (ET1). Subsequently, hippocampal samples were collected to analyze the levels of NLRP3/NF-κB, along with microglial activation in the hippocampus. Results: The results showed that ET1 injection induced depressive-like behaviors in a subset of rodents. However, a subset of mice showed no statistically significant differences from the control group in measures from the open field test (OFT), elevated plus maze (EPM), tail suspension test (TST), and forced swim test (FST), demonstrating depression resilience to PSD. Furthermore, PSD animals exhibited activated microglia and NLRP3/NF-κB activation, whereas these markers in the resilient group showed no significant difference compared to controls. Conclusions: This study provides evidence that depression resilience exists in a PSD model, and it suggests that the microglia–NLRP3 signaling axis may participate in this resilient phenotype. These findings offer potential intervention targets for the clinical prevention and treatment of PSD.