Department of Neurological Sciences University of Vermont Burlington VT USA.
Department of Obstetrics, Gynecology, and Reproductive Sciences University of Vermont Burlington VT USA.
J Am Heart Assoc. 2024 Jul 2;13(13):e035990. doi: 10.1161/JAHA.124.035990. Epub 2024 Jun 27.
Experimental preeclampsia (ePE) has been shown to have worsened outcome from stroke. We investigated the effect of low-dose aspirin, known to prevent preeclampsia, on stroke hemodynamics and outcome, and the association between the vasoconstrictor and vasodilator cyclooxygenase products thromboxane A and prostacyclin.
Middle cerebral artery occlusion was performed for 3 hours with 1 hour of reperfusion in normal pregnant rats on day 20 of gestation and compared with ePE treated with vehicle or low-dose aspirin (1.5 mg/kg per day). Multisite laser Doppler was used to measure changes in cerebral blood flow to the core middle cerebral artery and collateral vascular territories. After 30 minutes occlusion, phenylephrine was infused to increase blood pressure and assess cerebral blood flow autoregulation. Infarct and edema were measured using 2,3,5-triphenyltetrazolium chloride staining. Plasma levels of thromboxane A, prostacyclin, and inflammatory markers in plasma and cyclooxygenase levels in cerebral arteries were measured. ePE had increased infarction compared with normal pregnant rats (<0.05) that was reduced by aspirin (<0.001). ePE also had intact cerebral blood flow autoregulation and reduced collateral perfusion during induced hypertension that was also prevented by aspirin. Aspirin increased prostacyclin in ePE (<0.05) without reducing thromboxane B, metabolite of thromboxane A, or 8-isoprostane-prostaglandin-2α, a marker of lipid peroxidation. There were no differences in cyclooxygenase levels in cerebral arteries between groups.
Low-dose aspirin in ePE reduced infarction that was associated with increased vasodilator prostacyclin and improved collateral perfusion during induced hypertension. The beneficial effect of aspirin on the brain and cerebral circulation is likely multifactorial and worth further study.
实验性先兆子痫(ePE)已被证明会使中风的预后恶化。我们研究了小剂量阿司匹林对中风血液动力学和预后的影响,以及血管收缩剂和血管扩张剂环氧化酶产物血栓素 A 和前列环素之间的关联。
在妊娠第 20 天的正常孕鼠中进行大脑中动脉闭塞 3 小时,其中 1 小时再灌注,并与用载体或小剂量阿司匹林(每天 1.5mg/kg)治疗的 ePE 进行比较。多点激光多普勒用于测量核心大脑中动脉和侧支血管区域的脑血流变化。闭塞 30 分钟后,输注苯肾上腺素以增加血压并评估脑血流自动调节。使用 2,3,5-三苯基氯化四氮唑染色测量梗塞和水肿。测量血浆中血栓素 A、前列环素和炎症标志物的水平以及大脑动脉中环氧化酶的水平。与正常孕鼠相比,ePE 的梗塞增加(<0.05),而阿司匹林减少(<0.001)。ePE 在诱导性高血压期间也具有完整的脑血流自动调节和减少的侧支灌注,这也被阿司匹林预防。阿司匹林增加了 ePE 中的前列环素(<0.05),而没有减少血栓素 A 的代谢物血栓素 B 或脂质过氧化的标志物 8-异前列腺素-前列腺素 2α。各组之间大脑动脉中环氧化酶水平没有差异。
ePE 中的小剂量阿司匹林减少了梗塞,这与增加的血管扩张剂前列环素和诱导性高血压期间改善的侧支灌注有关。阿司匹林对大脑和脑循环的有益作用可能是多因素的,值得进一步研究。