Biology subjects

Acurio, J.

Publications and source records attributed to Acurio, J..

3 recordsLinked to original sources

bioRxiv2025

Sex-Specific Neurovascular and Cognitive Deficits in Offspring of Preeclampsia

BackgroundOffspring of preeclampsia may develop long-term neurovascular and cognitive impairments, but the underlying mechanisms remain unclear. We investigate sex-specific alterations in brain vascular function and cognition in a murine model of preeclampsia induced by the nitric oxide synthase inhibitor L-NAME. MethodsPregnant mice received L-NAME (gestational day 7 to 19). Offspring were assessed at postnatal day 5 (P5) and in adulthood (4-5 months). Brain vascular development, angiogenesis, perfusion, cold-induced vasoconstriction, and blood-brain barrier (BBB) integrity were assessed in vivo and ex vivo. Offsprings serum was applied to brain endothelial cell cultures to evaluate endothelial activation and barrier function. Adult cognitive performance was evaluated through behavioral tests and hippocampal long-term potentiation (LTP) recordings. ResultsL-NAME offspring (P5) exhibited reduced brain vascular density, decreased tip cell formation, and impaired cold-induced vasoconstriction, most prominently in males. BBB integrity was compromised, with increased permeability and reduced expression of tight junction proteins (claudin-5, ZO-1), again more pronounced in males. Serum from L-NAME offspring induced endothelial activation and barrier dysfunction in vitro. These effects were accompanied by increased brain and systemic levels of hypoxia markers and proinflammatory cytokines (IL-6, TNF-). Adult L-NAME offspring showed cognitive deficits in recognition and spatial memory tasks, with female offspring displaying more pronounced impairments. These behavioral findings paralleled a reduced magnitude and impaired stabilization of hippocampal LTP in females. ConclusionsPrenatal exposure to a preeclampsia-like environment induces persistent, sex-specific neurovascular and cognitive deficits in offspring. These findings underscore the need for long-term neurological follow-up in children born to preeclamptic pregnancies.

physiology↗

bioRxiv2025

Plasma, not extracellular vesicles, disrupts the blood-brain barrier in eclampsia.

BackgroundEclampsia 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. Magnesium sulfate (MgSO), the standard treatment, may mitigate BBB injury. We examined the effects of plasma and plasma-derived sEVs from women with eclampsia on BBB integrity and the potential modulatory role of MgSO. MethodsPlasma 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), Dextran 70 kDa permeability, and cytoskeletal alterations in the presence of womens plasmas or plasma-sEVs. The uptake of fluorescently labeled sEVs in the absence or pretreatment (-3 h) with MgSO, and sEVs cargo of relevant proteins involved in BBB regulation, were analyzed. ResultsPlasma 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. In contrast, plasma-sEVs of women with eclampsia caused less BBB impairment than plasma-sEVs from normotensive controls or preeclampsia, correlating with reduced sEVs uptake by brain endothelial cells. Lower levels of eNOS and TNF- in eclampsia-derived sEVs compared to normotensive controls were founnd. MgSO treatment further diminished sEVs uptake. ConclusionsPlasma, rather than sEVs, appears to drive BBB disruption in eclampsia. MgSO may influence these effects by reducing sEVs uptake and altering their protein cargo.

physiology↗

bioRxiv2024

Extracellular vesicles from preeclampsia disrupt the blood-brain barrier via reduced claudin-5: potential role of vascular endothelial growth factor

BackgroundPhysiopathology of life-treating cerebrovascular complications in preeclampsia are yet unknown. We investigated whether disruption of the blood-brain barrier (BBB), generated using circulating small extracellular vesicles (sEVs) from women with preeclampsia or placentae cultured under hypoxic conditions, impairs the expression of tight junction proteins, such as claudin 5 (CLDN5), mediated by VEGF and activation of VEGF receptor 2 (KDR). MethodssEVs were isolated from plasma (normal pregnancy, sEVs-NP, n=9); preeclampsia, sEVs-PE, n=9) or placental explants from normotensive pregnancies, cultured in normoxia (sEVs-Nor, n=10) or hypoxia (sEVs-Hyp, n=10). The integrity of the BBB was evaluated using in vitro (human and mice brain endothelial cell lines) and in vivo (non-pregnant C57BL/6 mice (4 to 5 months old, (n=10) were injected with sEVs-Hyp), models. ResultssEVs-PE and sEVs-Hyp reduced CLND5 levels (p<0.05) in the endothelial cell membrane without affecting other tight junction proteins. These results were negated with sEVs-PE sonication. sEVs-Hyp injected into non-pregnant mice generated neurological deficits and BBB disruption, specifically in the posterior area of the brain, associated with reduction in CLND5 levels in the brain cortex. Furthermore, sEVs-PE and sEVs-sHyp had higher VEGF levels than sEVs-NP and sEVs-Nor, respectively. Human brain endothelial cells exposed to sEVs-PE or sEVs-sHyp exhibited a reduction in the activation of KDR. ConclusionsEVs from hypoxic placentae and plasma from women with preeclampsia disrupt the BBB, via reduction of CLDN5, a phenomenon that may involve VEGF contained within these vesicles. These findings will improve the elucidation of cerebrovascular alterations in women with preeclampsia.

physiology↗