Maternal Aspirin Treatment Improves Ischemic Stroke Outcome in Adult Male Offspring From Experimental Preeclamptic...

Preeclampsia, a serious hypertensive disorder of pregnancy, is associated with increased long-term risk of cardiovascular disease in adult offspring, particularly stroke. Although low-dose aspirin (LDA) is used prophylactically to prevent preeclampsia, its impact on offspring is unclear. This study investigated the effect of maternal LDA treatment during experimental preeclampsia (ePE) on adult first-generation (F1) offspring, including stroke outcome.

ePE was induced in pregnant Sprague-Dawley rats via a high-cholesterol diet starting on gestational day 7 and treated with LDA (1.5 mg/kg) or vehicle. Offspring were weaned and fed standard chow until transient middle cerebral artery occlusion at 12 to 18 weeks (3-hour ischemia and 1-hour reperfusion). Fetal and juvenile weights were taken at gestational day 20 and from weeks 10 to 13. Infarct and edema were quantified using 2,3,5-triphenyltetrazolium chloride staining. Multisite laser Doppler was used to measure cerebral hemodynamics, including cerebral blood flow autoregulation and collateral flow. Circulating proinflammatory and anti-inflammatory factors were measured via multiplex immunoassay.

Male offspring from ePE dams (ePE-F1) had larger infarction and edema versus male offspring from normal pregnant dams (NormP-F1, 48%±6 versus 11%±4; P<0.01) and all female offspring. Maternal treatment with LDA was protective of male offspring (ePE+Asp-F1) that had reduced infarct and edema. Increased infarction in ePE-F1 males was associated with greater collateral perfusion deficit and elevated levels of TNF-α (tumor necrosis factor-alpha) and IL (interleukin)-1β that were prevented by maternal LDA treatment. There were no differences in infarct, edema, or perfusion deficit in female offspring.

Prenatal exposure to ePE worsened stroke severity and inflammation in male but not female offspring, which was largely mitigated by maternal LDA treatment, potentially due to an improved intrauterine environment. These findings highlight a sex-specific impact of prenatal preeclampsia exposure on long-term cerebrovascular health and suggest that maternal LDA may confer long-lasting protection to the offspring in addition to the mother.