Can Fibrinogen Drive Microglia Dysfunction?

Disruption of the blood-brain barrier (BBB) contributes to cerebral small vessel disease (cSVD) by facilitating plasma protein extravasation, including fibrinogen. Fibrinogen activates microglia into a pro-inflammatory state via CD11b/CD18 signaling. However, the effects of prolonged fibrinogen exposure on microglial function remain unclear. This study is the first to develop an in vitro model for cSVD by culturing BV-2 microglia for 7 days to investigate the impact of prolonged fibrinogen exposure, simulating conditions of chronic BBB disruption. The results demonstrated that repeated fibrinogen exposure induced sustained inflammation, oxidative stress, and a senescence-like phenotype in BV-2. Interestingly, prolonged in vitro culture alone resulted in dysfunction characterized by impaired mitochondrial function and senescence markers. This suggests that extended culture conditions can mimic aging-like effects on microglia. These findings highlight the dual impact of fibrinogen exposure and prolonged culture duration on microglial function, providing new insights for future studies on microglial dysfunction in cSVD.