Exposure to inflammation during pregnancy can predispose to brain injury in premature infants. In the present study, we investigated the effects of prolonged exposure to inflammation on the cerebrovasculature of preterm fetal sheep. Chronically instrumented fetal sheep at 103–104 days of gestation (full term is ~ 147 days) received continuous low-dose lipopolysaccharide (LPS) infusions (100 ng/kg over 24 h, followed by 250 ng/kg/24 h for 96 h plus boluses of 1 μg LPS at 48, 72, and 96 h) or the same volume of normal saline (0.9%, w/v). Ten days after the start of LPS exposure at 113–114 days of gestation, the sheep were killed, and the fetal brain perfused with formalin in situ. Vessel density, pericyte and astrocyte coverage of the blood vessels, and astrogliosis in the cerebral cortex and white matter were determined using immunohistochemistry. LPS exposure reduced (P < 0.05) microvascular vessel density and pericyte vascular coverage in the cerebral cortex and white matter of preterm fetal sheep, and increased the activation of perivascular astrocytes, but decreased astrocytic vessel coverage in the white matter. Prolonged exposure to LPS in preterm fetal sheep resulted in decreased vessel density and neurovascular remodeling, suggesting that chronic inflammation adversely affects the neurovascular unit and, therefore, could contribute to long-term impairment of brain development.

中文翻译：

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脂多糖诱导的早产羊脑神经血管单元的变化。

怀孕期间接触炎症会导致早产儿脑损伤。在本研究中，我们调查了长期暴露于炎症对早产胎羊脑血管系统的影响。妊娠 103-104 天（足月约 147 天）的慢性仪器化胎羊接受连续低剂量脂多糖 (LPS) 输注（100 ng/kg 超过 24 小时，然后是 250 ng/kg/24 小时，持续 96 小时加 1 μg LPS 在 48、72 和 96 小时推注）或相同体积的生理盐水（0.9%，w/v）。在妊娠 113-114 天开始暴露 LPS 后 10 天，羊被处死，胎儿大脑原位灌注福尔马林。使用免疫组织化学测定血管密度、血管周细胞和星形胶质细胞覆盖以及大脑皮层和白质中的星形胶质细胞增生。LPS暴露降低（P < 0.05）早产羊大脑皮层和白质的微血管密度和周细胞血管覆盖，并增加血管周围星形胶质细胞的活化，但减少了白质中的星形胶质细胞血管覆盖。早产胎羊长期暴露于 LPS 会导致血管密度降低和神经血管重塑，这表明慢性炎症会对神经血管单元产生不利影响，因此可能导致大脑发育的长期损害。