Aquaporin-1 regulates microglial polarization and inflammatory response in traumatic brain injury

The present study investigated the mechanisms by which aquaporin 1 (AQP1) influences microglial polarization and neuroinflammatory processes in traumatic brain injury (TBI). A model of TBI was generated in AQP1-knockout mice to assess the impact of AQP1 deletion on inflammatory cytokine release, neuronal damage and cognitive function. Immunofluorescence, reverse transcription-quantitative PCR, western blotting and enzyme-linked immunosorbent assay were employed to evaluate pro-inflammatory and anti-inflammatory markers. Behavioral assessments, including the Barnes maze, were performed to determine cognitive outcomes. Moreover, AQP1 knockout inhibited the activation of inflammation-related signaling pathways, including nuclear factor-kappa B, Janus kinase/signal transducer and activator of transcription, phosphoinositide 3-kinase/protein kinase B and extracellular signal-regulated kinase/mitogen-activated protein kinase pathways. Further studies indicated that the AQP1 inhibitor m-phenylenediacrylic acid demonstrated significant neuroprotective effects in a mouse model of TBI. These findings suggested that AQP1 may be essential in post-TBI inflammatory responses and neuronal injury, establishing a theoretical foundation for future therapies aimed at AQP1.