title: Plasma from patients with HELLP syndrome increases blood-brain barrier permeability.
abstract: Circulating inflammatory factors and endothelial dysfunction have been proposed to contribute to the pathophysiology of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. To date, the occurrence of neurological complications in these women has been reported, but few studies have examined whether impairment in blood-brain barrier (BBB) permeability or cerebrovascular reactivity is present in women having HELLP syndrome. We hypothesized that plasma from women with HELLP syndrome causes increased BBB permeability and cerebrovascular dysfunction. Posterior cerebral arteries from female nonpregnant rats were perfused with 20% serum from women with normal pregnancies (n = 5) or women with HELLP syndrome (n = 5), and BBB permeability and vascular reactivity were compared. Plasma from women with HELLP syndrome increased BBB permeability while not changing myogenic tone and reactivity to pressure. Addition of the nitric oxide (NO) synthase inhibitor N(ω)-nitro-L-arginine methyl ester caused constriction of arteries that was not different with the different plasmas nor was dilation to the NO donor sodium nitroprusside different between the 2 groups. However, dilation to the small- and intermediate-conductance, calcium-activated potassium channel activator NS309 was decreased in vessels exposed to HELLP plasma. Thus, increased BBB permeability in response to HELLP plasma was associated with selective endothelial dysfunction.
authors.affiliation: Department of Obstetrics & Gynecology, University of Mississippi Medical Center, Jackson, MS, USA kwallace2@umc.edu.
authors.forename: Kedra
authors.initials: K
authors.lastname: Wallace
authors.affiliation: Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, USA Department of Obstetrics, Gynecology & Reproductive Sciences, University of Vermont College of Medicine, Burlington, VT, USA Department of Pharmacology, University of Vermont College of Medicine, Burlington, VT, USA.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Tremble
authors.affiliation: Department of Obstetrics & Gynecology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Michelle Y
authors.initials: MY
authors.lastname: Owens
authors.affiliation: Department of Obstetrics & Gynecology, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Rachael
authors.initials: R
authors.lastname: Morris
authors.affiliation: Department of Neurological Sciences, University of Vermont College of Medicine, Burlington, VT, USA Department of Obstetrics, Gynecology & Reproductive Sciences, University of Vermont College of Medicine, Burlington, VT, USA Department of Pharmacology, University of Vermont College of Medicine, Burlington, VT, USA.
authors.forename: Marilyn J
authors.initials: MJ
authors.lastname: Cipolla
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002199:Capillary Permeability; D016022:Case-Control Studies; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D017359:HELLP Syndrome / Q000097:blood* / Q000503:physiopathology; D006801:Humans; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D020769:Posterior Cerebral Artery / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D011247:Pregnancy; D017207:Rats, Sprague-Dawley; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D055815:Young Adult
chemical_list: D004791:Enzyme Inhibitors; D051660:Intermediate-Conductance Calcium-Activated Potassium Channels; D020030:Nitric Oxide Donors; D051640:Small-Conductance Calcium-Activated Potassium Channels; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase
keywords: HELLP syndrome; blood–brain barrier permeability; myogenic response