Blood–Brain Barrier Breakdown in Reduced Uterine Perfusion Pressure: A Possible Model of Posterior Reversible Encephalopathy Syndrome

Marrone, Luiz Carlos Porcello; Gadonski, Giovani; Laguna, Gabriela de Oliveira; Poli-de-Figueiredo, Carlos Eduardo; Costa, Bartira Ercí­lia Pinheiro da; Lopes, M F; Brunelli, João Pedro Farina; Diogo, Luciano Passamani; Marrone, A.; Costa, Jaderson Costa da

doi:10.1016/j.jstrokecerebrovasdis.2014.03.012

Cited by 22 publications

(16 citation statements)

References 19 publications

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“…Thus, the use of 70 kDa Texas red dextran that does not bind to albumin likely provides more reliable results. Further, the two studies reporting increased BBB permeability to Evan's Blue in RUPP rats allowed the tracer to circulate for a longer duration of time: 3–24 hours versus 10 minutes in the current study [49] , [50] . These longer time frames likely provide more variable results due to differences in clearance by cerebrospinal fluid or other tissues, including placenta [55] – [57] .…”

Section: Discussionmentioning

confidence: 83%

“…The lack of increase in permeability to large solutes is in contrast to two recent studies using the RUPP model without high cholesterol treatment. Both studies report increased BBB permeability to Evan's Blue in RUPP compared to pregnant control rats [49] , [50] . One explanation of these contrasting results is the different methodology used.…”

Section: Discussionmentioning

confidence: 95%

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Magnesium Sulfate Treatment Reverses Seizure Susceptibility and Decreases Neuroinflammation in a Rat Model of Severe Preeclampsia

et al. 2014

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Eclampsia, defined as unexplained seizure in a woman with preeclampsia, is a life-threatening complication of pregnancy with unclear etiology. Magnesium sulfate (MgSO4) is the leading eclamptic seizure prophylactic, yet its mechanism of action remains unclear. Here, we hypothesized severe preeclampsia is a state of increased seizure susceptibility due to blood-brain barrier (BBB) disruption and neuroinflammation that lowers seizure threshold. Further, MgSO4 decreases seizure susceptibility by protecting the BBB and preventing neuroinflammation. To model severe preeclampsia, placental ischemia (reduced uteroplacental perfusion pressure; RUPP) was combined with a high cholesterol diet (HC) to cause maternal endothelial dysfunction. RUPP+HC rats developed symptoms associated with severe preeclampsia, including hypertension, oxidative stress, endothelial dysfunction and fetal and placental growth restriction. Seizure threshold was determined by quantifying the amount of pentylenetetrazole (PTZ; mg/kg) required to elicit seizure in RUPP+HC±MgSO4 and compared to normal pregnant controls (n = 6/group; gestational day 20). RUPP+HC rats were more sensitive to PTZ with seizure threshold being ∼65% lower vs. control (12.4±1.7 vs. 36.7±3.9 mg/kg PTZ; p<0.05) that was reversed by MgSO4 (45.7±8.7 mg/kg PTZ; p<0.05 vs. RUPP+HC). BBB permeability to sodium fluorescein, measured in-vivo (n = 5–7/group), was increased in RUPP+HC vs. control rats, with more tracer passing into the brain (15.9±1.0 vs. 12.2±0.3 counts/gram ×1000; p<0.05) and was unaffected by MgSO4 (15.6±1.0 counts/gram ×1000; p<0.05 vs. controls). In addition, RUPP+HC rats were in a state of neuroinflammation, indicated by 35±2% of microglia being active compared to 9±2% in normal pregnancy (p<0.01; n = 3–8/group). MgSO4 treatment reversed neuroinflammation, reducing microglial activation to 6±2% (p<0.01 vs. RUPP+HC). Overall, RUPP+HC rats were in a state of augmented seizure susceptibility potentially due to increased BBB permeability and neuroinflammation. MgSO4 treatment reversed this, increasing seizure threshold and decreasing neuroinflammation, without affecting BBB permeability. Thus, reducing neuroinflammation may be one mechanism by which MgSO4 prevents eclampsia during severe preeclampsia.

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Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 95%

Magnesium Sulfate Treatment Reverses Seizure Susceptibility and Decreases Neuroinflammation in a Rat Model of Severe Preeclampsia

et al. 2014

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“…24 Animal models of PEC have demonstrated impaired cerebral autoregulation, increased blood-brain barrier permeability, and neuronal hyperexcitability, mediated by elevated levels of tumor necrosis factor- alpha . 25–28 In the setting of PEC-associated inflammation and puerperial hypercoagulability, superimposed infection could trigger stroke by exacerbating inflammation and coagulopathy. 11 …”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Pregnancy-Associated Stroke in Women With Preeclampsia

Miller

Gatollari

Too

et al. 2017

Stroke

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Background and Purpose Preeclampsia (PEC) affects 3–8% of pregnancies, and increases risk of pregnancy-associated stroke (PAS). Data are limited on which women with PEC are at highest risk for PAS. Methods Using billing data from the 2003–2012 New York State Department of Health inpatient database, we matched women with PEC and PAS 1:3 to preeclamptic controls based on age and race/ethnicity. Pre-defined PAS risk factors included pregnancy complications, infection present on admission, vascular risk factors, prothrombotic states, and coagulopathies. We constructed multivariable conditional logistic regression models to calculate the odds ratios and 95% confidence intervals (OR, 95%CI) for independent risk factors for PAS. Results Among women aged 12–55 years admitted to New York State hospitals for any reason during the study period (n= 3,373,114), 88,857 had PEC, 197 of whom (0.2%) had PAS. In multivariable analysis, women with PEC and stroke were more likely than controls to have severe PEC or eclampsia (OR 7.2, 95%CI 4.6–11.3), infections present on admission (OR 3.0, 95%CI 1.6–5.8), prothrombotic states (OR 3.5, 95%CI 1.3–9.2), coagulopathies (OR 3.1, 95%CI 1.3–7.1), or chronic hypertension (OR 3.2, 95%CI 1.8–5.5). Additional analyses matched and stratified by severity of PEC confirmed these results. Conclusions Infections, chronic hypertension, coagulopathies, and underlying prothrombotic conditions increase PAS risk in women with PEC. These women may warrant closer monitoring.

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“… 1 There are two prevailing hypotheses: cytotoxic and vasogenic. 4 5 Eclampsia, renal failure, autoimmune diseases, and chemotherapy treatment and other factors may trigger PRES. 1 5 Despite its classically favorable outcome, PRES is associated with direct mortality in 5-15% of cases.…”

mentioning

confidence: 99%

Malignant Posterior Reversible Encephalopathy Syndrome: A Case of Posterior Irreversible Encephalopathy Syndrome

Martins

Marrone

2016

J Clin Neurol

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Blood–Brain Barrier Breakdown in Reduced Uterine Perfusion Pressure: A Possible Model of Posterior Reversible Encephalopathy Syndrome

Cited by 22 publications

References 19 publications

Magnesium Sulfate Treatment Reverses Seizure Susceptibility and Decreases Neuroinflammation in a Rat Model of Severe Preeclampsia

Magnesium Sulfate Treatment Reverses Seizure Susceptibility and Decreases Neuroinflammation in a Rat Model of Severe Preeclampsia

Risk Factors for Pregnancy-Associated Stroke in Women With Preeclampsia

Malignant Posterior Reversible Encephalopathy Syndrome: A Case of Posterior Irreversible Encephalopathy Syndrome

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