Cyclosporin A ameliorates eclampsia seizure through reducing systemic inflammation in an eclampsia-like rat model

Huang, Qian; Hu, Bihui; Han, Xinjia; Yang, Jinying; Di, Xiaodan; Bao, Junjie; Liu, Huishu

doi:10.1038/s41440-019-0387-3

Cited by 8 publications

(5 citation statements)

References 41 publications

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“…The precise mechanism underlying this increased permeability is unclear, although inflammation has been blamed. Consistent with these observations, markers of inflammation such as C-reactive protein levels, Tumor Necrosis Factor -alpha (TNF-α) are elevated in Preeclampsia [42][43][44]. The pattern of edema seen in preeclampsia and eclampsia appears to resemble that in the posterior reversible encephalopathy syndrome (PRES) which can complicate some cases of this disorder [45][46][47].…”

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confidence: 75%

Cardio-Renal & Neurologic Complications of Preeclampsia: Current Concepts & Clinical Implications

2024

J Preg Child Health

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Preeclampsia, which afflicts 3-5% of pregnancies worldwide, has recently being recognized to be a cardio-renal syndrome, in which neurologic complications contribute to the morbidity and mortality of this syndrome. The precise pathogenesis of preeclampsia, itself, is not definitely elucidated, but an imbalance of angiogenic & anti-angiogenic factors appear at play. The acute neurologic complications of preeclampsia such as seizures, cerebral edema, stroke, and posterior reversible leukoencephalopathy syndrome (PRES) are the leading contributors to obstetric mortality and morbidity in many low to middle and some high income countries. In addition to these acute devastating complications, registry and other long-term data, over recent decades now reveal that chronic neurologic & cardiovascular complications in the mothers as well as the offspring of preeclamptic pregnancies also contribute to future morbidity. In this review, we evaluate putative biophysical mechanisms of these cardio-renal and neurologic complications in both mother & child, as well as clinical implications of these new findings. We outline a rational monitoring strategy for these late complications in preeclamptic mothers & children born from preeclamptic pregnancies. Preventive strategies, encompassing aspirin, calcium-vitamin D supplementation, exercise, pravastatin, and metformin, offer insights into mitigating preeclampsia risks. Active management, balancing antihypertensives and planned delivery, appears to yield positive outcomes. Future pathways emphasize advancements in pathogenesis research, early predictive biomarkers, personalized therapeutic approaches, and global health initiatives. The role of wearable devices, telemedicine, and continuous monitoring in maternal-fetal health surveillance is paramount. Specific attention to unraveling neurological complications and establishing long-term follow-up programs is crucial for comprehensive care.

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confidence: 75%

Cardio-Renal & Neurologic Complications of Preeclampsia: Current Concepts & Clinical Implications

2024

J Preg Child Health

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“…However, the sources of elevated circulating SASP, placenta and/or other tissues (such as adipose tissue), remain unclear and will be the topic of our future studies. We extended studies of senescence to MSC, multipotent cells that play critical roles in normal pregnancy through stimulation of angiogenesis, immune tolerance of the semi-allogeneic foetus, and anti-inflammatory effects, [ 23 , 24 ] including downregulation of TNF-α and stimulation of IL-10. We recently demonstrated that the number of senescent cells, as determined by senescence-associated beta-galactosidase staining, was significantly higher in PE-MSC compared to NT-MSC.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic and senescence markers indicate an accelerated ageing-like state in women with preeclamptic pregnancies

et al. 2021

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Background: Preeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria and/or multisystem involvement. Disease-specific therapy has yet to be developed due to the lack of understanding of underlying mechanism(s). We postulate that accelerated ageing in general, and particularly cellular senescence, play a role in its pathophysiology. Methods: We compared women with preeclampsia vs. normotensive pregnancies with respect to epigenetic markers of ageing and markers of senescence in tissues/organs affected by preeclampsia (blood, urine, adipose tissue, and kidney). Findings: We demonstrate that preeclamptic compared to normotensive pregnant women: (i) undergo accelerated epigenetic ageing during pregnancy, as demonstrated by an "epigenetic clock"; (ii) exhibit higher levels/expression of senescence-associated secretory phenotype factors in blood and adipose tissue; (iii) display increased expression of p16 INK4A in adipose tissue and renal sections, and (iv) demonstrate decreased levels of urinary a-Klotho (an anti-ageing protein) at the time of delivery. Finally, we provide data indicating that pre-treatment with dasatinib, a senolytic agent, rescues the angiogenic potential of mesenchymal stem cells (MSC) obtained from preeclamptic pregnancies, and promotes angiogenesis, even under pro-inflammatory conditions. Interpretation: Taken together, our results identify senescence as one of the mechanisms underpinning the pathophysiology of preeclampsia. Therapeutic strategies that target senescent cells may offer novel mechanism-based treatments for preeclampsia.

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“…In addition, CsA treatment significantly reduced the inflammatory cytokine levels and improved pregnancy outcomes following eclampsia-like seizures. The decreased inflammatory cytokines in PE are coincident with attenuated PE manifestation, suggesting that CsA treatment might decrease the PE severity through decreasing systemic inflammation [ 41 ]. Crocin, a hydrophilic carotenoid pigment, is a major compound with pharmacological activities found in Crocus sativus L. (saffron).…”

Section: Managementmentioning

confidence: 99%

Preeclampsia up to date—What’s going on?

Bokuda

Ichihara

2023

Hypertens Res

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Preeclampsia is a hypertensive disorder in pregnancy characterized by placental malperfusion and subsequent multi-organ injury. It accounts for approximately 14% of maternal deaths and 10–25% of perinatal deaths globally. In addition, preeclampsia has been attracting attentions for its association with risks for developing chronic diseases in later life for both mother and child. This mini-review discusses on latest knowledge on prediction, prevention, management, and long-term outcomes of preeclampsia and also touches on association between COVID-19 and preeclampsia. HTN hypertension, HDP hypertensive disorders of pregnancy, PE preeclampsia, BP blood pressure, cfDNA cell-free DNA, ST2 human suppression of tumorigenesis 2, sFlt-1 soluble fms-like tyrosine kinase-1, PIGF placental growth factor, VEGF vascular endothelial growth factor, VEGFR VEGF receptor, TGF β transforming growth factor β , ENG endoglin, sENG soluble ENG, PRES posterior reversible encephalopathy syndrome, AKI acute kidney injury, CVD cardiovascular disease, ESKD end-stage kidney disease, ACE angiotensinogen converting enzyme, Ang angiotensin.

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Cyclosporin A ameliorates eclampsia seizure through reducing systemic inflammation in an eclampsia-like rat model

Cited by 8 publications

References 41 publications

Cardio-Renal & Neurologic Complications of Preeclampsia: Current Concepts & Clinical Implications

Cardio-Renal & Neurologic Complications of Preeclampsia: Current Concepts & Clinical Implications

Epigenetic and senescence markers indicate an accelerated ageing-like state in women with preeclamptic pregnancies

Preeclampsia up to date—What’s going on?

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