Mouse offspring exposed to preeclampsia/eclampsia-like symptoms exhibit cerebral hypoperfusion and mild cognitive impairment at 2 mo of age.

Preeclampsia is a pregnancy complication characterized by high blood pressure and signs of organ damage, after the 20th week of pregnancy. Children born to mothers with preeclampsia or eclampsia (new-onset seizures during pregnancy) are more likely to develop learning and memory deficits and are more susceptible to neurovascular diseases compared with those born from normal pregnancies. The contributing mechanisms are unknown. In this study, we assessed whether exposure to reduced uteroplacental perfusion (RUPP), modeling placental hypoperfusion and preeclampsia, with or without pentylenetetrazol (PTZ) injection (to induce seizures and model eclampsia), results in cognitive impairment, Alzheimer's disease markers, and regional cerebral perfusion changes in adult offspring. On gestational day (GD)13.5, pregnant C57BL/6 mice (n = 22) underwent Sham or RUPP surgery followed by injection or no treatment with PTZ (40 mg/kg) on GD18.5. At 2 mo of age, spatial learning and cerebral perfusion were measured in randomly selected offspring or averaged to obtain mean data per sex, per litter (n = 4-6 data points per group/treatment). RUPP-exposed offspring took a longer distance and made more errors navigating the Barnes maze. Cerebral perfusion was reduced in offspring exposed to RUPP, specifically in the prefrontal cortex, superior sagittal sinus, and whole brain. There was a significant reduction in perfusion in seizure-exposed offspring in the superior sagittal and transverse sinuses, whole brain, and cerebellum. Our results support the hypothesis that exposure to preeclampsia/eclampsia-like symptoms leads to mild learning impairment through reduced cerebral perfusion to cortical regions and decreased drainage of waste from the brain via the cerebral sinuses.NEW & NOTEWORTHY This is the first study to assess vascular-related cognitive function and Alzheimer's disease markers in young adult mice exposed to preclinical preeclampsia and eclampsia-like conditions. We show that mild learning impairments occur in the presence of cerebral hypoperfusion and reduced venous drainage into the brain sinuses. We also report that as early as 2 mo of age, Alzheimer's disease markers are increased in the brains of offspring exposed to seizures.