Differential short-term regional effects of early high dose erythropoietin on white matter in preterm lambs after mechanical ventilation
Differential short-term regional effects of early high dose erythropoietin on white matter in preterm lambs after mechanical ventilation
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DOI：
10.1113/jp271376
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发表时间：
2016-03-01
影响因子：
5.5
通讯作者：
Tolcos, Mary
中科院分区：
文献类型：
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作者：
Barton, Samantha K.;McDougall, Annie R. A.;Tolcos, Mary
关键点id=“tjp 6825-list-0001”list-type=“bulleted促红细胞生成素是一种神经保护剂，正在对足月儿和早产儿的脑损伤进行临床试验。这是第一个实验研究，以评估促红细胞生成素对早产儿通气羔羊大脑白色物质的急性影响。促红细胞生成素在损伤性通气发作几分钟内的给药分娩室中早产儿的意外损伤性通气可引起脑白色物质（WM）炎症和损伤。我们研究了早期高剂量的重组人促红细胞生成素（EPO）对早产羔羊通气诱导的WM变化的影响。对早产羔羊（妊娠0.85）进行伤害性通气，目标是V-T为15 mlkg（-1），无呼气末正压，持续15分钟。继续常规通气105 min。羔羊在42分钟时通过脐静脉接受5000 IU kg（-1）EPO（EPREX（R）; Vent+EPO; n=6）或载体（Vent; n=8）。使用定量实时PCR（qPCR）和免疫组化评估WM损伤和炎症的标志物，并与一组未通气对照组（UVC; n=4）进行比较。与Vent组相比，Vent+EPO组：（1）脑室周围WM中IL-1和IL-6 mRNA水平以及皮质下WM中IL-8 mRNA水平均显著升高（P
Key points id="tjp6825-list-0001" list-type="bulleted Erythropoietin is a neuroprotectant undergoing clinical trial for brain injury in term and preterm infants. This is the first experimental study to assess the acute effects of erythropoietin on the cerebral white matter in preterm ventilated lambs. Administration of erythropoietin within minutes of injurious ventilation onset Inadvertently injurious ventilation of preterm neonates in the delivery room can cause cerebral white matter (WM) inflammation and injury. We investigated the impact of an early high dose of recombinant human erythropoietin (EPO) on ventilation-induced WM changes in preterm lambs. Injurious ventilation, targeting a V-T of 15mlkg(-1) with no positive end-expiratory pressure, was initiated for 15min in preterm lambs (0.85 gestation). Conventional ventilation was continued for a further 105min. Lambs received either 5000IUkg(-1) of EPO (EPREX (R); Vent+EPO; n=6) or vehicle (Vent; n=8) via an umbilical vein at 42min. Markers of WM injury and inflammation were assessed using quantitative real-time PCR (qPCR) and immunohistochemistry and compared to a group of unventilated controls (UVC; n=4). In Vent+EPO lambs compared to Vent lambs: (i) interleukin (IL)-1 and IL-6 mRNA levels in the periventricular WM and IL-8 mRNA levels in the subcortical WM were higher (P