Department of Anatomy and Cell Biology, University of Melbourne, Victoria, Australia.
J Neuropathol Exp Neurol. 2010 Mar;69(3):306-19. doi: 10.1097/NEN.0b013e3181d27138.
Intrauterine infection and inflammation have been linked to preterm birth and brain damage. We hypothesized that recombinant human erythropoietin (rhEPO) would ameliorate brain damage in anovine model of fetal inflammation. At 107 +/- 1 day of gestational age (DGA), chronically catheterized fetal sheep received on 3 consecutive days 1) an intravenous bolus dose of lipopolysaccharide ([LPS] approximately 0.9 microg/kg; n = 8); 2) an intravenous bolus dose of LPS, followed at 1 hour by 5,000 IU/kg of rhEPO (LPS + rhEPO, n = 8); or 3) rhEPO (n = 5). Untreated fetuses (n = 8) served as controls. Fetal physiological parameters were monitored, and fetal brains and optic nerves were histologically examined at 116 +/- 1 DGA. Exposure to LPS, but not to rhEPO alone or saline, resulted in fetal hypoxemia, hypotension (p < 0.05), brain damage, including white matter injury, and reductions in numbers of myelinating oligodendrocytes in the corticospinal tract and myelinated axons in the optic nerve (p < 0.05 for both). Treatment of LPS-exposed fetuses with rhEPO did not alter the physiological effects of LPS but reduced brain injury and was beneficial to myelination in the corticospinal tract and the optic nerve. This is the first study in a long-gestation species to demonstrate the neuroprotective potential of rhEPO in reducing fetal brain and optic nerve injury after LPS exposure.
宫内感染和炎症与早产和脑损伤有关。我们假设重组人促红细胞生成素（rhEPO）将改善胎儿炎症的羊模型中的脑损伤。在妊娠 107 +/- 1 天（DGA）时，长期导管化的胎儿羊在连续 3 天内接受以下处理：1）静脉内给予脂多糖（[LPS]约 0.9 微克/公斤；n = 8）；2）静脉内给予 LPS，1 小时后给予 5000IU/kg rhEPO（LPS + rhEPO，n = 8）；或 3）rhEPO（n = 5）。未治疗的胎儿（n = 8）作为对照。监测胎儿生理参数，并在 116 +/- 1 DGA 时对胎儿大脑和视神经进行组织学检查。LPS 暴露而不是 rhEPO 单独或盐水暴露导致胎儿低氧血症、低血压（p < 0.05）、脑损伤，包括白质损伤，以及皮质脊髓束中的少突胶质细胞数量减少和视神经中的髓鞘化轴突（p < 0.05）。用 rhEPO 治疗 LPS 暴露的胎儿不会改变 LPS 的生理效应，但可减轻脑损伤，并有利于皮质脊髓束和视神经中的髓鞘形成。这是在长妊娠物种中首次研究 rhEPO 在减少 LPS 暴露后胎儿脑和视神经损伤中的神经保护潜力。
