Plasma From Preeclamptic Women Increases Blood-Brain Barrier Permeability

Amburgey, Ödül A.; Chapman, Abbie C.; May, Víctor; Bernstein, Ira M.; Cipolla, Marilyn J.

doi:10.1161/hypertensionaha.110.158931

Cited by 108 publications

(113 citation statements)

References 33 publications

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“…A recent study demonstrated an increased blood-brain barrier permeability of 6.5-and 18-fold when exposed to normal pregnant (median of 34 weeks gestation) plasma and pre-eclamptic plasma, respectively. 16 With a combination of pathologic and potentially physiologic changes, it seems likely that the penetration of rituximab to the CNS lymphoma in our patient greatly exceeded that previously reported in the literature, despite a suggestion by some that dexamethasone can decrease the permeability of the blood-brain barrier. This is supported by the dramatic and immediate response experienced by our patient after experiencing progressive symptoms during treatment with highdose corticosteroids.…”

contrasting

confidence: 69%

Single-Agent Rituximab for Primary CNS Lymphoma During Pregnancy As a Bridge to Definitive Management

Burnette

Jentoft

Porrata

et al. 2014

JCO

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A 30-year-old female at 22 weeks gestation with her third child presented in February 2008 with a 10-day history of episodic imbalance with left-sided tonic-clonic activity without loss of consciousness. The episodes were followed by a progressive frontal headache. Initial exam was unremarkable, but a noncontrast magnetic resonance imaging (MRI) of the head demonstrated a large region of T2 hyperintensity in the white matter extending from the anterior right lateral ventricle to the right frontal lobe. A second region of T2 hyperintensity with mild mass effect extended from the superior-posterior right ventricle to the right frontal lobe ( Fig 1A). As the evaluation was ongoing, the patient developed new weakness of the left arm and leg. A biopsy of the right frontal lobe demonstrated a CD20-positive diffuse large B-cell lymphoma that was Epstein-Barr virus negative (Figs 2A and 2B).Dexamethasone 4 mg three times daily was initiated after biopsy at week 24, but the patient developed progressive weakness after 4 days. Exam demonstrated 1 of 5 (with 5 being normal) strength of the left hip and knee flexors, 2 of 5 of the left lower extremity dorsiflexors and plantar flexors, and 2 of 5 of the left deltoids. She was unable to ambulate. It was clear that there was tumor progression despite steroids and that alternative therapy for her primary CNS lymphoma (PCNSL) was urgently needed. A comprehensive multidisciplinary discussion was held with the patient and her family regarding the risks and potential benefits of high-dose methotrexate to her and the 25-week-old fetus. The patient was offered the choice of terminating pregnancy or proceeding with treatment for her PCNSL. Ultimately, the patient elected to continue the pregnancy and attempt to control her disease with the anti-CD20 monoclonal antibody rituximab as the fetus matured to viability. The plan was to initiate high-dose chemotherapy with methotrexate (HD-MTX) if there was any evidence of progression or even lack of response to rituximab.Rituximab 375 mg/m 2 was initiated at week 25, and dexamethasone 4 mg three times daily was continued. Within 12 hours, the weakness in her left upper extremity had resolved, and the weakness in

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contrasting

confidence: 69%

Single-Agent Rituximab for Primary CNS Lymphoma During Pregnancy As a Bridge to Definitive Management

Burnette

Jentoft

Porrata

et al. 2014

JCO

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“…In addition, hydraulic conductivity, an important parameter that relates water movement through the vessel wall in response to hydrostatic pressure, is normally very low in cerebral endothelial cells due to the high electrical resistance tight junctions and low pinocytotic activity (72). Similar to paracellular and transcellular permeability, hydraulic conductivity is not changed during pregnancy (24) but is increased in response to preeclamptic plasma (2). Increased hydraulic conductivity during preeclampsia could promote neurological symptoms since increased BBB permeability has been linked to several pathological states, including preeclampsia and eclampsia, as well as epilepsy (55,56,63).…”

Section: The Cerebral Endothelium and Bbbmentioning

confidence: 99%

“…For example, vascular endothelial growth factor (VEGF), a cytokine originally named vascular permeability factor, is secreted by the placenta and elevated during pregnancy in the uteroplacental unit and the maternal circulation (2,14,19,37). VEGF interacts with its receptors VEGFR1 [or FMS-like tyrosine kinase receptor 1 (Flt-1)] and VEGFR2 [or fetal liver kinase 1 (Flk-1)] located on vascular endothelium to initiate several critical physiological processes involved in angiogenesis, vascular growth, and endothelial cell survival (34,76).…”

Section: The Cerebral Endothelium and Bbbmentioning

confidence: 99%

The Cerebral Circulation During Pregnancy: Adapting to Preserve Normalcy

Johnson

Cipolla

2015

Physiology

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The adaptation of the brain and cerebral circulation to pregnancy are unique compared with other organs and circulatory systems, ultimately functioning to maintain brain homeostasis. In this review, the effect of pregnancy on critical functions of the cerebral circulation is discussed, including changes occurring at the endothelium and blood-brain barrier, and changes in the structure and function of cerebral arteries and arterioles, hemodynamics, and cerebral blood flow autoregulation. The brain is an organ of high metabolic demand that consumes ϳ20% of the body's oxygen at rest, despite comprising only 2% of body weight (77). Importantly, the brain has a relatively narrow capacity to tolerate changes in ion and water balance, and blood flow (77). The brain is also unique in that it is enclosed in a rigid skull, and therefore increased vascular permeability or volume could result in detrimentally increased intracranial pressure that can cause serious neurological symptoms, brain herniation, and even death. Thus there is a need to maintain tight control of cerebral blood flow (CBF) and water flux in the face of a 40 -50% increase in plasma volume and cardiac output during pregnancy and a decline in systemic vascular resistance necessary for the maintenance of a healthy blood pressure (28). In contrast to other organs outside the central nervous system that undergo substantial increases in both perfusion and transvascular filtration during pregnancy, including the uterus, kidney, and heart, the cerebral circulation must resist these adaptations to counterbalance global hemodynamic changes to maintain the delicate microenvironment of the brain. Thus the adaptation of the brain and cerebral circulation to pregnancy appears to be to maintain normalcy despite substantial hormonal and cardiovascular changes in almost every other organ. Throughout this review, the effect of pregnancy on several aspects of the cerebral circulation will be discussed, including the cerebral endothelium and blood-brain barrier (BBB), the structure and function of the cerebrovasculature, hemodynamics, and CBF autoregulation. Furthermore, in the context of these cerebrovascular adaptations, the risk for neurological complications that arises in women with preeclampsia, a dangerous hypertensive complication of pregnancy, will be considered. Preeclampsia affects 3-8% of all pregnancies and is defined as the appearance of hypertension and proteinuria after week 20 of gestation. Many organs are affected by preeclampsia, including the brain, putting women at risk of seizure and hemorrhage. In fact, the cerebral circulation has a central role in neurological complications of preeclampsia, and thus understanding how pregnancy and preeclampsia affect the cerebrovasculature is of interest. Vasomotor Responses to Circulating FactorsOne of the most important adaptations of the cerebral circulation during pregnancy is to counteract the effects of circulating vasoactive factors. During pregnancy, large amounts of hormones are secreted from the placenta, ...

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“…However, their results cannot be extrapolated to preeclamptic patients as magnesium transfer to the CSF might differ in pre-eclampsia. One may postulate that pre-eclamptic changes in vascular permeability might allow magnesium to cross the blood brain barrier (8), but there are few reports exploring that theory. In their study comparing CSF magnesium levels in healthy and pre-eclamptic parturients not receiving magnesium therapy, Fong et al (10) did not find any difference.…”

Section: Discussionmentioning

confidence: 99%