Perinatal hypoxic-ischemic (HI)-related brain injury is an important cause of morbidity and long-standing disability in newborns. The only currently approved therapeutic strategy available to reduce brain injury in the newborn is hypothermia. Therapeutic hypothermia can only be used to treat HI encephalopathy in full-term infants and survivors remain at high risk for a wide spectrum of neurodevelopmental abnormalities as a result of residual brain injury. Therefore, there is an urgent need for adjunctive therapeutic strategies. Inflammation and neurovascular damage are important factors that contribute to the pathophysiology of HI-related brain injury and represent exciting potential targets for therapeutic intervention. In this review, we address the role of each component of the neurovascular unit (NVU) in the pathophysiology of HI-related injury in the neonatal brain. Disruption of the blood-brain barrier (BBB) observed in the early hours after an HI-related event is associated with a response at the basal lamina level, which comprises astrocytes, pericytes, and immune cells, all of which could affect BBB function to further exacerbate parenchymal injury. Future research is required to determine potential drugs that could prevent or attenuate neurovascular damage and/or augment repair. However, some studies have reported beneficial effects of hypothermia, erythropoietin, stem cell therapy, anti-cytokine therapy and metformin in ameliorating several different facets of damage to the NVU after HI-related brain injury in the perinatal period.

中文翻译：

---

新生儿大脑缺氧缺血相关的脑血管变化和潜在的治疗策略。


围产期缺氧缺血（HI）相关脑损伤是新生儿发病和长期残疾的重要原因。目前唯一批准的可减少新生儿脑损伤的治疗策略是低温治疗。低温治疗只能用于治疗足月婴儿的 HI 脑病，幸存者因残余脑损伤而仍面临广泛神经发育异常的高风险。因此，迫切需要辅助治疗策略。炎症和神经血管损伤是导致 HI 相关脑损伤病理生理学的重要因素，也是治疗干预的令人兴奋的潜在目标。在这篇综述中，我们探讨了神经血管单元 (NVU) 各组成部分在新生儿脑损伤相关病理生理学中的作用。在 HI 相关事件发生后的几个小时内观察到的血脑屏障 (BBB) 破坏与基底层水平的反应有关，基底层水平包括星形胶质细胞、周细胞和免疫细胞，所有这些都可能影响 BBB 功能，从而进一步加剧实质损伤。未来的研究需要确定可以预防或减轻神经血管损伤和/或增强修复的潜在药物。然而，一些研究报告了低温、促红细胞生成素、干细胞治疗、抗细胞因子治疗和二甲双胍在改善围产期 HI 相关脑损伤后 NVU 几个不同方面的损伤方面的有益作用。