BACKGROUND Neonatal ventilation exacerbates brain injury in lambs with fetal growth restriction (FGR), characterized by neuroinflammation and reduced blood-brain barrier integrity, which is normally maintained by the neurovascular unit. We examined whether umbilical cord blood stem cell (UCBC) treatment stabilized the neurovascular unit and reduced brain injury in preterm ventilated FGR lambs. METHODS Surgery was performed in twin-bearing pregnant ewes at 88 days' gestation to induce FGR in one fetus. At 127 days, FGR and appropriate for gestational age (AGA) lambs were delivered, carotid artery flow probes and umbilical lines inserted, lambs intubated and commenced on gentle ventilation. Allogeneic ovine UCBCs (25 × 106 cells/kg) were administered intravenously to lambs at 1 h of life. Lambs were ventilated for 24 h and then euthanized. RESULTS FGR (n = 6) and FGR+UCBC (n = 6) lambs were growth restricted compared to AGA (n = 6) and AGA+UCBC (n = 6) lambs (combined weight, FGR 2.3 ± 0.4 vs. AGA 3.0 ± 0.3 kg; p = 0.0002). UCBC therapy did not alter mean arterial blood pressure or carotid blood flow but decreased cerebrovascular resistance in FGR+UCBC lambs. Circulating TNF-α cytokine levels were lower in FGR+UCBC vs. FGR lambs (p < 0.05). Brain histopathology showed decreased neuroinflammation and oxidative stress, increased endothelial cell proliferation, pericyte stability, and greater integrity of the neurovascular unit in FGR+UCBC vs. FGR lambs. CONCLUSIONS Umbilical cord blood stem cell therapy mitigates perinatal brain injury due to FGR and ventilation, and the neuroprotective benefits may be mediated by stabilization of the neurovascular unit.

中文翻译：

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脐带血干细胞在生长受限的新生羔羊中的神经血管作用：UCBCs用于围产期脑损伤。

背景技术新生儿通气加重了胎儿生长受限（FGR）的羔羊的脑损伤，胎儿生长受限（FGR）的特征在于神经炎症和血脑屏障完整性的降低，这通常由神经血管单元维持。我们检查了脐带血干细胞（UCBC）治疗是否能稳定早产通气FGR羔羊的神经血管单位并减少其脑损伤。方法：对双胎妊娠母羊在妊娠88天时进行手术，以诱导其胎儿的FGR。在第127天，交付了FGR和适合胎龄（AGA）的羔羊，插入了颈动脉流量探针和脐带，插管了羔羊，并开始进行通气。异体绵羊UCBCs（25×106细胞/ kg）在生命的1小时内静脉注射给羔羊。将羔羊通风24小时，然后实施安乐死。结果与AGA（n = 6）和AGA + UCBC（n = 6）羔羊相比，FGR（n = 6）和FGR + UCBC（n = 6）羔羊受生长限制（组合重量，FGR 2.3±0.4 vs. AGA 3.0 ±0.3公斤； p = 0.0002）。UCBC治疗并未改变FGR + UCBC羔羊的平均动脉血压或颈动脉血流，但降低了其脑血管阻力。与FGR羔羊相比，FGR + UCBC的循环TNF-α细胞因子水平较低（p <0.05）。脑组织病理学显示，FGR + UCBC与FGR羔羊相比，FGR + UCBC的神经炎和氧化应激降低，内皮细胞增殖增加，周细胞稳定性提高，并且神经血管单位的完整性更高。结论脐带血干细胞疗法可减轻由于FGR和通气引起的围产期脑损伤，并且神经保护作用可以通过稳定神经血管单位来介导。