Perinatal Micro-Bleeds and Neuroinflammation in E19 Rat Fetuses Exposed to Utero-Placental Ischemia
Perinatal Micro-Bleeds and Neuroinflammation in E19 Rat Fetuses Exposed to Utero-Placental Ischemia
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DOI：
10.3390/ijms20164051
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发表时间：
2019-08-02
影响因子：
5.6
通讯作者：
Warrington, Junie P.
中科院分区：
文献类型：
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作者：
Giambrone, Ashtin B.;Logue, Omar C.;Warrington, Junie P.
先兆子痫患者的后代发生神经功能缺损和认知障碍的风险增加。虽然低胎盘灌注（常见于先兆子痫和生长受限）与神经功能缺陷有关，但因果关系尚未完全确定。本研究的目的是检验胎盘缺血诱导子宫内神经炎症和微血管生成的假设。将定时妊娠的Sprague道利大鼠进行假手术（仅腹部切口）或诱导的胎盘缺血（子宫胎盘灌注的手术减少（RUPP））的体重匹配;在妊娠第14天，n = 5/组。在胚胎日（E19）采集胎脑（n = 1-2/母体/终点）。胎盘缺血导致活胎减少，胎仔死亡率增加，红细胞压积增加，暴露胎仔的脑含水量无差异。此外，在暴露于RUPP的胎儿中观察到脑微出血（用H&E染色鉴定）、促炎细胞因子：IL-1 β、IL-6和IL-18、嗜酸性粒细胞趋化因子（CCL 11）、LIX（CXCL 5）和MIP-2（CXCL 2）增加。暴露于RIPP的胎儿脑室下区的小胶质细胞密度降低，皮质厚度无变化。我们的研究结果支持这一假设，即暴露于胎盘缺血有助于微血管功能障碍（增加微出血），胎儿脑炎症，并减少小胶质细胞密度在增殖脑区。未来的研究将确定子宫内异常是否通过受损的神经发生调节导致先兆子痫后代的长期行为缺陷。
Offspring of preeclampsia patients have an increased risk of developing neurological deficits and cognitive impairment. While low placental perfusion, common in preeclampsia and growth restriction, has been linked to neurological deficits, a causative link is not fully established. The goal of this study was to test the hypothesis that placental ischemia induces neuroinflammation and micro-hemorrhages in utero. Timed-pregnant Sprague Dawley rats were weight-matched for sham surgery (abdominal incision only) or induced placental ischemia (surgical reduction of utero-placental perfusion (RUPP)); n = 5/group on gestational day 14. Fetal brains (n = 1-2/dam/endpoint) were collected at embryonic day (E19). Placental ischemia resulted in fewer live fetuses, increased fetal demise, increased hematocrit, and no difference in brain water content in exposed fetuses. Additionally, increased cerebral micro-bleeds (identified with H&E staining), pro-inflammatory cytokines: IL-1 beta, IL-6, and IL-18, eotaxin (CCL11), LIX (CXCL5), and MIP-2 (CXCL2) were observed in RUPP-exposed fetuses. Microglial density in the sub-ventricular zone decreased in RUPP-exposed fetuses, with no change in cortical thickness. Our findings support the hypothesis that exposure to placental ischemia contributes to microvascular dysfunction (increased micro-bleeds), fetal brain inflammation, and reduced microglial density in proliferative brain areas. Future studies will determine whether in utero abnormalities contribute to long-term behavioral deficits in preeclampsia offspring through impaired neurogenesis regulation.