Stroke in Pregnancy and Preeclampsia: Effect of Low‐Dose Aspirin Treatment on Collateral Flow Velocity and Cerebral Blood Flow Autoregulation During Ischemia in Rats

Background 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 t...

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Main Authors: Marilyn J. Cipolla, Sarah M. Tremble
Format: Article
Language:English
Published: Wiley 2024-07-01
Series:Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
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Online Access:https://www.ahajournals.org/doi/10.1161/JAHA.124.035990
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author Marilyn J. Cipolla
Sarah M. Tremble
author_facet Marilyn J. Cipolla
Sarah M. Tremble
author_sort Marilyn J. Cipolla
collection DOAJ
description Background 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 A2 and prostacyclin. Methods and Results 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 A2, prostacyclin, and inflammatory markers in plasma and cyclooxygenase levels in cerebral arteries were measured. ePE had increased infarction compared with normal pregnant rats (P<0.05) that was reduced by aspirin (P<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 (P<0.05) without reducing thromboxane B2, metabolite of thromboxane A2, or 8‐isoprostane‐prostaglandin‐2α, a marker of lipid peroxidation. There were no differences in cyclooxygenase levels in cerebral arteries between groups. Conclusions 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.
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spelling doaj-art-2784ab909cb043c3ab86ed61cdff6cc32025-08-20T02:26:32ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-07-01131310.1161/JAHA.124.035990Stroke in Pregnancy and Preeclampsia: Effect of Low‐Dose Aspirin Treatment on Collateral Flow Velocity and Cerebral Blood Flow Autoregulation During Ischemia in RatsMarilyn J. Cipolla0Sarah M. Tremble1Department of Neurological Sciences University of Vermont Burlington VT USADepartment of Neurological Sciences University of Vermont Burlington VT USABackground 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 A2 and prostacyclin. Methods and Results 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 A2, prostacyclin, and inflammatory markers in plasma and cyclooxygenase levels in cerebral arteries were measured. ePE had increased infarction compared with normal pregnant rats (P<0.05) that was reduced by aspirin (P<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 (P<0.05) without reducing thromboxane B2, metabolite of thromboxane A2, or 8‐isoprostane‐prostaglandin‐2α, a marker of lipid peroxidation. There were no differences in cyclooxygenase levels in cerebral arteries between groups. Conclusions 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.https://www.ahajournals.org/doi/10.1161/JAHA.124.035990cerebral blood flow autoregulationinfarctionischemic strokepreeclampsiaprostacyclin
spellingShingle Marilyn J. Cipolla
Sarah M. Tremble
Stroke in Pregnancy and Preeclampsia: Effect of Low‐Dose Aspirin Treatment on Collateral Flow Velocity and Cerebral Blood Flow Autoregulation During Ischemia in Rats
Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
cerebral blood flow autoregulation
infarction
ischemic stroke
preeclampsia
prostacyclin
title Stroke in Pregnancy and Preeclampsia: Effect of Low‐Dose Aspirin Treatment on Collateral Flow Velocity and Cerebral Blood Flow Autoregulation During Ischemia in Rats
title_full Stroke in Pregnancy and Preeclampsia: Effect of Low‐Dose Aspirin Treatment on Collateral Flow Velocity and Cerebral Blood Flow Autoregulation During Ischemia in Rats
title_fullStr Stroke in Pregnancy and Preeclampsia: Effect of Low‐Dose Aspirin Treatment on Collateral Flow Velocity and Cerebral Blood Flow Autoregulation During Ischemia in Rats
title_full_unstemmed Stroke in Pregnancy and Preeclampsia: Effect of Low‐Dose Aspirin Treatment on Collateral Flow Velocity and Cerebral Blood Flow Autoregulation During Ischemia in Rats
title_short Stroke in Pregnancy and Preeclampsia: Effect of Low‐Dose Aspirin Treatment on Collateral Flow Velocity and Cerebral Blood Flow Autoregulation During Ischemia in Rats
title_sort stroke in pregnancy and preeclampsia effect of low dose aspirin treatment on collateral flow velocity and cerebral blood flow autoregulation during ischemia in rats
topic cerebral blood flow autoregulation
infarction
ischemic stroke
preeclampsia
prostacyclin
url https://www.ahajournals.org/doi/10.1161/JAHA.124.035990
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AT sarahmtremble strokeinpregnancyandpreeclampsiaeffectoflowdoseaspirintreatmentoncollateralflowvelocityandcerebralbloodflowautoregulationduringischemiainrats