Oxidative memory in microglia: persistent OSI-driven polarization and ıts modulation by mitochondrial dynamics (Mdivi-1).

We evaluated sustained effects of transient H₂O₂ exposure on the oxidative stress index (OSI) and polarization signatures in BV2 microglia, and compared modulation of mitochondrial dynamics by Mdivi‑1 (a putative DRP1‑linked modulator) with antioxidant buffering by N‑acetylcysteine (NAC), carefully under defined conditions. BV2 cells were exposed to H₂O₂ (50 µM, 2 h). Selected arms received 1 h pretreatment with Mdivi‑1 (25 µM) or NAC (5 mM). Doses reflected literature demonstrating robust redox modulation. Dose selection prioritized efficacy with maintained viability. OSI (TOS/TAC) was assessed at 2, 24, and 72 h. Readouts included transcriptional markers (RT‑qPCR), cytokines (ELISA), and viability (WST‑1). Seventy‑two hours was the primary endpoint to test persistence beyond the acute window; 2 h and 24 h were descriptive. Analysis focused on durability at 72 h. Groups contained n = 6 biological replicates. Transient H₂O₂ increased OSI and induced a proinflammatory profile persisting through 24-72 h, with decreased P2ry12 and elevated Nos2/Arg1 ratio and Il1b. Mdivi‑1 improved the phenotype without fully normalizing OSI; it increased P2ry12, lowered the Nos2/Arg1 ratio and Il1b, and improved IL‑6/TNF‑α and viability versus elevated‑OSI. NAC reduced oxidative load but conferred less phenotypic recovery than Mdivi‑1. Viability remained > 80%, consistent with a sublethal stress model. Taken together, these findings indicate that a brief oxidative challenge is associated with a persistent redox-inflammatory bias in BV2 microglia that remains detectable beyond the acute exposure window. Within this experimental setting, Mdivi-1 was associated with broader phenotypic recovery than NAC, while mechanistic conclusions regarding mitochondrial dynamics remain interpretive.