Microglial proximity stabilizes capillary sprouts for cerebral angiogenesis during chronic hypoxia adaptation

Microglia are key players in the reconstruction of cerebral microvascular networks, predominantly via releasing angiogenic factors. Here we show their role in the adaptation of microvascular networks to chronic hypoxia in the adult mouse somatosensory cortex with long-term two-photon microscopy imaging. Despite mild morphological changes, the microglial cell number decreases, while cellular translocation significantly increases. We find that microglial process proximity correlates with capillary sprout fate. The sprouts closely associated with microglia eventually connect to existing capillaries. Pharmacological reduction of the microglia population shows a downward trend in the connection rate of newly formed sprouts, consistent with a supportive role for microglia in sprout stabilization. Furthermore, minocycline treatment, which suppresses general microglial activation, does not significantly alter the formation of new capillary networks, suggesting the stabilization role is independent of inflammatory processes. These findings redefine microglia as key structural components required for capillary sprout stabilization, suggesting a potential therapeutic strategy to promote cerebral microvascular network reconstruction. Microglial process proximity stabilizes capillary sprouts during hypoxia-induced angiogenesis, independent of inflammatory signaling, redefining microglia as active structural components essential for microvascular network reconstruction.