Kropf Ari, Anderson Jennifer L, Esposito Milena, Tremble Sarah M, Cipolla Marilyn J
Department of Neurological Sciences, University of Vermont Larner College of Medicine, Burlington, VT, USA.
Department of Biology, Ecology and Earth Science, University of Calabria, Rende, Italy.
Neuroprotection. 2025 Jun;3(2):172-182. doi: 10.1002/nep3.70002. Epub 2025 Apr 13.
Preeclampsia (PE) is a serious hypertensive disorder of pregnancy that has lifelong deleterious effects, including increased risk of stroke postpartum (PP). Here we determined if previous PE exacerbates ischemic injury in the PP period and investigated underlying mechanisms including oxidative stress and collateral perfusion.
Female Sprague-Dawley rats were studied at 4-9 months PP, after either a normal pregnancy (NormP-PP = 7) or experimental PE (ePE) induced via high cholesterol diet during gestation (ePE-PP = 9). Animals underwent transient middle cerebral artery occlusion (tMCAO) for 2 hours with 1 hour reperfusion. Dual-site laser Doppler flowmetry measured changes in cerebral blood flow (CBF) in the MCA and collateral territories. Ischemic injury was measured by 2,3,5-triphenyl tetrazolium chloride staining. Circulating 8-isoprostane, 3-nitrotyrosine (3-NT), and oxidized low-density lipoprotein (oxLDL) were measured by enzyme-linked immunosorbent assays. In separate groups of animals, NormP-PP ( = 10) and ePE-PP ( = 9) that were 3-4 months PP, isolated pial collateral vessels, leptomeningeal anastomoses (LMAs), and mesenteric arteries were studied using pressure myography.
Previous ePE pregnancy worsened stroke outcome in the PP state, significantly increasing infarction in ePE-PP vs. NormP-PP animals (40.6 ± 7.6% vs. 13.7 ± 6.5%; <0.01) and edema (5.1 ± 2.0% vs. 2.6 ± 0.4%; < 0.01), despite comparable changes in CBF in both MCA and pial collateral territories during ischemia and reperfusion. When infarction was analyzed as a function of perfusion deficit, ePE-PP animals had greater sensitivity to ischemia. Pial collaterals had increased pressure-induced myogenic tone vs. NormP-PP rats. Percent tone at 80 mmHg for ePE-PP vs. NormP-PP was 15.5 ± 1.6% vs. 8.6 ± 1.9% ( <0.01). In addition, ePE-PP animals had significantly elevated circulating 8-isoprostane and 3-NT, but not oxLDL, after tMCAO (*<0.05 and **<0.01, respectively).
We found worsened stroke outcome after ePE pregnancy that was related to increased sensitivity to ischemia, increased pial collateral tone, and elevated levels of oxidative stress markers. Thus, the pathologic effects of ePE persisted PP and negatively impacted stroke outcome.
子痫前期（PE）是一种严重的妊娠高血压疾病，具有终身有害影响，包括产后（PP）中风风险增加。在此，我们确定既往子痫前期是否会在产后时期加重缺血性损伤，并研究包括氧化应激和侧支循环灌注在内的潜在机制。
对产后4 - 9个月的雌性Sprague-Dawley大鼠进行研究，这些大鼠在妊娠期间经历了正常妊娠（NormP-PP = 7）或通过高胆固醇饮食诱导的实验性子痫前期（ePE）（ePE-PP = 9）。动物接受大脑中动脉短暂闭塞（tMCAO）2小时，再灌注1小时。双位点激光多普勒血流仪测量大脑中动脉（MCA）和侧支循环区域的脑血流量（CBF）变化。通过2,3,5 - 三苯基氯化四氮唑染色测量缺血性损伤。通过酶联免疫吸附测定法测量循环中的8 - 异前列腺素、3 - 硝基酪氨酸（3 - NT）和氧化型低密度脂蛋白（oxLDL）。在另一组动物中，对产后3 - 4个月的NormP-PP（ = 10）和ePE-PP（ = 9）大鼠，使用压力肌动描记法研究分离的软脑膜侧支血管、软脑膜吻合支（LMA）和肠系膜动脉。
既往ePE妊娠使产后状态下的中风结局恶化，与NormP-PP动物相比，ePE-PP动物的梗死面积显著增加（40.6±7.6%对13.7±6.5%；<0.01）和水肿（5.1±2.0%对2.6±0.4%；<0.01），尽管在缺血和再灌注期间MCA和软脑膜侧支区域的CBF变化相当。当将梗死面积作为灌注不足的函数进行分析时，ePE-PP动物对缺血更敏感。与NormP-PP大鼠相比，软脑膜侧支的压力诱导肌源性张力增加。ePE-PP在80 mmHg时的张力百分比与NormP-PP相比为15.5±1.6%对8.6±1.9%（<0.01）。此外，tMCAO后，ePE-PP动物的循环8 - 异前列腺素和3 - NT显著升高，但oxLDL未升高（分别为*<0.05和**<0.01）。
我们发现ePE妊娠后中风结局恶化，这与对缺血的敏感性增加、软脑膜侧支张力增加以及氧化应激标志物水平升高有关。因此，ePE的病理影响在产后持续存在，并对中风结局产生负面影响。
