Stojanovska Vanesa, Barton Samantha K, Tolcos Mary, Gill Andrew W, Kluckow Martin, Miller Suzanne L, Zahra Valerie, Hooper Stuart B, Galinsky Robert, Polglase Graeme R
The Ritchie Centre, Hudson Institute of Medical Research, Melbourne, Victoria, Australia.
Department of Obstetrics and Gynaecology, Monash University, Melbourne, Victoria, Australia.
Dev Neurosci. 2018;40(5-6):497-507. doi: 10.1159/000496466. Epub 2019 Mar 6.
Antenatal administration of betamethasone (BM) is a common antecedent of preterm birth, but there is limited information about its impact on the acute evolution of preterm neonatal brain injury. We aimed to compare the effects of maternal BM in combination with mechanical ventilation on the white matter (WM) of late preterm sheep. At 0.85 of gestation, pregnant ewes were randomly assigned to receive intra-muscular (i.m.) saline (n = 9) or i.m. BM (n = 13). Lambs were delivered and unventilated controls (UVCSal, n = 4; UVCBM, n = 6) were humanely killed without intervention; ventilated lambs (VentSal, n = 5; VentBM, n = 7) were injuriously ventilated for 15 min, followed by conventional ventilation for 75 min. Cardiovascular and cerebral haemodynamics and oxygenation were measured continuously. The cerebral WM underwent assessment of inflammation and injury, and oxidative stress was measured in the cerebrospinal fluid (CSF). In the periventricular and subcortical WM tracts, the proportion of amoeboid (activated) microglia, the density of astrocytes, and the number of blood vessels with protein extravasation were higher in UVCBM than in UVCSal (p < 0.05 for all). During ventilation, tidal volume, mean arterial pressure, carotid blood flow, and oxygen delivery were higher in -VentBM lambs (p < 0.05 vs. VentSal). In the subcortical WM, microglial infiltration was increased in the VentSal group compared to UVCSal. The proportion of activated microglia and protein extravasation was higher in the VentBM group compared to VentSal within the periventricular and subcortical WM tracts (p < 0.05). CSF oxidative stress was increased in the VentBM group compared to UVCSal, UVCBM, and VentSal groups (p < 0.05). Antenatal BM was associated with inflammation and vascular permeability in the WM of late preterm fetal sheep. During the immediate neonatal period, the increased carotid perfusion and oxygen delivery in BM-treated lambs was associated with increased oxidative stress, microglial activation and microvascular injury.
产前给予倍他米松（BM）是早产的常见诱因，但关于其对早产新生儿脑损伤急性进展的影响的信息有限。我们旨在比较母体BM联合机械通气对晚期早产绵羊白质（WM）的影响。在妊娠0.85时，将怀孕母羊随机分为接受肌肉注射（i.m.）生理盐水（n = 9）或i.m. BM（n = 13）。羔羊出生后，未通气对照组（UVCSal，n = 4；UVCBM，n = 6）在无干预的情况下被人道处死；通气羔羊（VentSal，n = 5；VentBM，n = 7）进行有害通气15分钟，然后进行常规通气75分钟。连续测量心血管和脑血流动力学及氧合情况。对脑白质进行炎症和损伤评估，并测量脑脊液（CSF）中的氧化应激。在脑室周围和皮质下白质束中，UVCBM组中阿米巴样（活化）小胶质细胞的比例、星形胶质细胞的密度以及有蛋白外渗的血管数量均高于UVCSal组（所有p < 0.05）。在通气期间，VentBM组羔羊的潮气量、平均动脉压、颈动脉血流量和氧输送量均较高（与VentSal组相比，p < 0.05）。与UVCSal组相比，VentSal组皮质下白质中的小胶质细胞浸润增加。在脑室周围和皮质下白质束中，VentBM组活化小胶质细胞的比例和蛋白外渗高于VentSal组（p < 0.05）。与UVCSal组、UVCBM组和VentSal组相比，VentBM组脑脊液氧化应激增加（p < 0.05）。产前BM与晚期早产胎儿绵羊白质中的炎症和血管通透性有关。在新生儿早期，BM治疗的羔羊颈动脉灌注和氧输送增加与氧化应激增加、小胶质细胞活化和微血管损伤有关。
