Pericytes play essential roles in blood-brain barrier integrity and their dysfunction is implicated in neurological disorders such as stroke although the underlying mechanisms remain unknown. Hypoxia-inducible factor-1 (HIF-1), a master regulator of injury responses, has divergent roles in different cells especially during stress scenarios. On one hand HIF-1 is neuroprotective but on the other it induces vascular permeability. Since pericytes are critical for barrier stability, we asked if pericyte HIF-1 signaling impacts barrier integrity and injury severity in a mouse model of ischemic stroke. We show that pericyte HIF-1 loss of function (LoF) diminishes ischemic damage and barrier permeability at 3 days reperfusion. HIF-1 deficiency preserved barrier integrity by reducing pericyte death thereby maintaining vessel coverage and junctional protein organization, and suppressing vascular remodeling. Importantly, considerable improvements in sensorimotor function were observed in HIF-1 LoF mice indicating that better vascular functionality post stroke improves outcome. Thus, boosting vascular integrity by inhibiting pericytic HIF-1 activation and/or increasing pericyte survival may be a lucrative option to accelerate recovery after severe brain injury.

周细胞在血脑屏障完整性中起重要作用，其功能障碍与中风等神经系统疾病有关，尽管其潜在机制仍不清楚。缺氧诱导因子 1 (HIF-1) 是损伤反应的主要调节因子，在不同的细胞中具有不同的作用，尤其是在应激情况下。一方面 HIF-1 具有神经保护作用，但另一方面它诱导血管通透性。由于周细胞对屏障稳定性至关重要，我们询问周细胞 HIF-1 信号是否会影响缺血性中风小鼠模型中的屏障完整性和损伤严重程度。我们表明，周细胞 HIF-1 功能丧失 (LoF) 在 3 天再灌注时会减少缺血性损伤和屏障通透性。HIF-1 缺乏通过减少周细胞死亡来保持屏障完整性，从而维持血管覆盖和连接蛋白组织，并抑制血管重塑。重要的是，在 HIF-1 LoF 小鼠中观察到感觉运动功能的显着改善，表明卒中后更好的血管功能可改善预后。因此，通过抑制周细胞 HIF-1 活化和/或增加周细胞存活来增强血管完整性可能是加速严重脑损伤后恢复的有利选择。