Abstract Body: Introduction: Offspring from preeclamptic women are at increased risk of neurologic disorders later in life and have an increased risk of death from stroke. We hypothesized that the unfavorable intrauterine environment during preeclampsia (PE) causes cerebrovascular dysfunction and inflammation in offspring that worsens stroke outcome.
Methods: Adult male and female offspring (n=6-8/group) from Sprague Dawley rats that had normal pregnancies (NormP-F1) or experimental PE (ePE-F1) underwent transient MCA occlusion (tMCAO) for 3 hours with 1 hour of reperfusion. Blood gases were kept within normal ranges. Multisite laser Doppler was used to measure changes in pial collateral flow and MCA cerebral blood flow (CBF) simultaneously. Infarct and edema were measured by TTC staining. After tMCAO, plasma was obtained to measure circulating inflammatory factors using Multiplex and ELISA. Data are reported as mean±SEM.
Results: Offspring from ePE dams had elevated blood glucose, and sex-specific increases in infarct and edema—only ePE-F1 males had significantly larger infarcts compared to all other groups (48.0±5.7% vs. 9.0±1.3% ePE-F1 female, 10.9±3.9% NormP-F1 male, and 4.9±1.9% NormP-F1 female). The rate of hemorrhagic transformation (HT) was increased in both ePE-F1 males (100%) and females (62.5%) vs. NormP-F1s (male: 37.5%, female: 0%). The increased infarct in ePE-F1 males was associated with poor collateral flow, decreasing -59.8±3.3% which remained low during the ischemic period. In contrast collateral flow decreased -43.9±17.8% in ePE-F1 females that was not sustained and increased to baseline after 40 min of tMCAO. Both female and male NormP-F1’s had robust collateral flow, decreasing only -14.8±25.5% and -17.5±22.1%, respectively. There was an increase in circulating VEGF in ePE-F1 males vs NormP-F1 males (188.8±69.3 vs 39.2±7.5 pg/ml; p<0.05) but not between females. The concentration of the proinflammatory cytokine IL-1β and the anti-inflammatory cytokine IL-10 were increased in ePE-F1 males vs. NormP-F1 males (119.3±17.8 vs 35.3±7.7 and 765.4±83.8 vs 356.4±62.6 pg/ml; p<0.05) indicating an inflammatory mechanism not present in other groups.
Conclusion: These data demonstrate the far-reaching effects of adverse pregnancy in PE that worsens stroke outcome in offspring. The mechanisms by which PE negatively impacts offspring in a sexually dimorphic manner is unclear but may be related to (epi)-genetic programming in utero on cerebrovascular development.