In vitro evidence that plasma of women with eclampsia disrupts the blood-brain barrier

Background Eclampsia is a severe complication of preeclampsia involving blood-brain barrier (BBB) disruption. While small extracellular vesicles (sEVs) contribute to endothelial dysfunction in preeclampsia, their role in eclampsia remains unclear. We examined the effects of plasma and plasma-derived sEVs from women with eclampsia on BBB integrity. Methods Plasma and plasma-sEVs were isolated from women with normotensive pregnancies (n=18), preeclampsia (n=19), preeclampsia with organ complications (n=17), and eclampsia (n=20). An in vitro BBB model based on the culture of human brain endothelial cells was used to evaluate electrical resistance (TEER) and Dextran 70 kDa permeability in the presence of women’s plasmas or plasma-sEVs. sEVs cargo of relevant proteins involved in BBB regulation, eNOS, and TNF-α, were analyzed. Results Plasma from women with eclampsia disrupted the BBB, with marked reductions in TEER and increased permeability compared to normotensive controls, preeclampsia, and preeclampsia with organ complications. Moreover, plasma-sEVs of women with eclampsia caused a drop in TEERs but less BBB permeability than plasma-sEVs from normotensive controls or preeclampsia. Lower levels of eNOS and TNF-α in eclampsia-derived sEVs compared to normotensive controls were found. Conclusions We report the critical role of circulating plasma factors in the disruption of the BBB during eclampsia. Although plasma-derived sEVs induce some alterations in barrier properties, our findings suggest they are not the main drivers of the BBB impairment observed in eclampsia, likely due to altered cargo composition.