Pre-eclampsia leaves a lasting impact by worsening stroke outcomes postpartum in rats

Pre-eclampsia (PE), a serious hypertensive disorder that affects approximately 3–8% of pregnant women, is known to have long-lasting effects on the maternal vascular system. Women with a history of PE face a higher risk of developing conditions such as hypertension, hyperlipidemia, and even early-onset cognitive impairments later in life. Since PE causes widespread endothelial dysfunction, one concerning outcome is its potential to increase the risk of developing severe cerebrovascular complications, including stroke, in the postpartum period. However, how PE impacts the cerebral vasculature after childbirth remains unclear.

Previous studies in animal models of hypertension have shown that impaired cerebral vascular circulation worsens stroke outcomes. However, it remains uncertain whether similar circulatory impairments persist postpartum in individuals with a history of PE and whether these could lead to more severe stroke-related damage.

To address this gap, a team of researchers led by Professor Marilyn J. Cipolla from the University of Vermont, USA, induced experimental PE in rat models and studied the effects of a transient cerebral artery occlusion (or stroke) in them. Their findings were published in the journal Neuroprotection on 13 April, 2025.

“In the present study, we aimed to determine whether a history of PE impairs collateral recruitment and worsens ischemic stroke outcomes,” explains Prof. Cipolla. The team used female Sprague-Dawley rats, randomly divided them into two groups: one group was fed a normal diet during pregnancy (NormP-PP), while the other received a high-cholesterol diet to induce PE (ePE-PP). Stroke was induced in both groups 4 to 9 months after delivery to examine the effects of prior PE. In addition, a separate set of postpartum rats from each group that were not subjected to stroke were examined to assess differences in cerebrovascular function.

The study revealed that rats with a history of PE (ePE-PP) had significantly worse stroke outcomes compared to their NormP-PP counterparts. This included increased infarct size and cerebral edema. Further analysis showed that infarct severity in the ePE-PP group was more closely related to reductions in blood perfusion, indicating a higher sensitivity to cerebral ischemia. Prof. Cipolla explains, “PE is associated with high levels of circulating oxidative stress markers, which may persist postpartum. Thus, we determined whether markers of oxidative stress were present in the PP period in response to stroke, and whether these markers were increased in ePE-PP rats.” In line with their hypothesis, ePE-PP rats showed significantly elevated levels of oxidative stress markers in the blood were significantly higher in the ePE-PP group than in the NormP-PP group, suggesting that persistent oxidative stress may contribute to worse stroke outcomes in individuals with a history of PE.

The researchers also analyzed the behavior of small arteries on the surface of the brain known as  pial collaterals, which can provide alternate routes for blood flow in the event of a stroke. They found that these vessels exhibited greater pressure-induced constriction (myogenic tone) in ePE-PP rats. Moreover, the vessel diameters in this group were notably smaller in their active (contracted) state compared to the passive (relaxed) state across various pressure conditions—an abnormal response not seen in the NormP-PP rats.

Taken together, the findings indicate that PE has long-lasting adverse effects on the brain’s vascular network, even months after pregnancy. The ePE-PP rats not only experienced more severe strokes but also showed increased vulnerability to ischemia and sustained oxidative stress, alongside abnormal responses in key blood vessels involved in collateral circulation. “Understanding the underlying mechanisms of PE's effects on the cerebrovasculature, both during the index pregnancy and months to years postpartum, may lead to the development of interventions for preventing stroke and improving cardiovascular outcomes in this vulnerable population,” concludes Prof. Cipolla.

With further research into the prolonged impact of PE on maternal brain health, scientists may be able to uncover new ways to reduce stroke injury and enhance long-term well-being for women affected by this condition.

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Reference

DOI: 10.1002/nep3.70002

About Professor Marilyn J. Cipolla

Marilyn J. Cipolla is a Professor of Neurology at the University of Vermont Larner College of Medicine, USA. She received a MS in cell and molecular biology in 1994 followed by a PhD in cell and molecular biology in 1997 from the University of Vermont. Prof. Cipolla's area of expertise is in Reproductive Biology, Pharmacology, cerebrovacsulature during stroke, and acute hypertension. She has over 200 publications to her credit, and has mentored several projects in these disciplines.

Funding
National Institute of General Medical Sciences, Grant/Award Number: P20 GM135007‐04S1; National Institute of Neurological Disorders and Stroke, Grant/Award Number: R01NS093289