Background and Purpose-Magnesium sulfate is used extensively for prevention of eclamptic seizures. Empirical and clinical evidence supports the effectiveness of magnesium sulfate; however, questions remain as to its safety and mechanism. This review summarizes current evidence supporting the possible mechanisms of action and several controversies for magnesium sulfate treatment. Summary of Review-Several mechanisms are presented, including the effects of magnesium sulfate on peripheral and cerebral vasodilation, blood-brain barrier protection, and as an anticonvulsant. Conclusions-Though the specific mechanisms of action remain unclear, the effect of magnesium sulfate in the prevention of eclampsia is likely multi-factorial. Magnesium sulfate may act as a vasodilator, with actions in the peripheral vasculature or the cerebrovasculature, to decrease peripheral vascular resistance or relieve vasoconstriction. Additionally, magnesium sulfate may also protect the blood-brain barrier and limit cerebral edema formation, or it may act through a central anticonvulsant action.

A detailed analysis of peptide backbone amide (H(N)) and H alpha chemical shifts reveals a consistent pattern for beta hairpins and three-stranded beta sheets. The H alpha's at non-hydrogen-bonded strand positions are inwardly directed and shifted downfield approximately 1 ppm due largely to an anisotropy contribution from the cross-strand amide function. The secondary structure associated H alpha shift deviations for the H-bonded strand positions are also positive but much smaller (0.1-0.3 ppm) and the turn residues display negative H alpha chemical shift deviations (CSDs). The pattern of (H(N)) shift deviations is an even better indicator of both hairpin formation and register, with the cross-strand H-bonded sites shifted downfield (also by approximately 1 ppm) and with diagnostic values for the first turn residue and the first strand position following the turn. These empirical observations, initially made for [2:2]/[2:4]-type-I' and -II' hairpins, are rationalized and can be extended to the analysis of other turns, hairpin classes ([3:5], [4:4]/[4:6]), and three-stranded peptide beta-sheet models. The H alpha's at non-hydrogen-bonded sites and (H(N))'s in the intervening H-bonded sites provide the largest and most dependable measures of hairpin structuring and can be used for melting studies; however the intrinsic temperature dependence of (H(N)) shifts deviations needs to reflect the extent of solvent sequestration in the folded state. Several observations made in the course of this study provide insights into beta-sheet folding mechanisms: (1) The magnitude of the (H(N)) shifts suggests that the cross-strand H-bonds in peptide hairpins are as short as those in protein beta sheets. (2) Even L-Pro-Gly turns, which are frequently used in unfolded controls for hairpin peptides, can support hairpin populations in aqueous fluoroalcohol media. (3) The good correlation between hairpin population estimates from cross-strand H-bonded (H(N)) shift deviations, H alpha shift deviations, and structuring shifts at the turn locus implies that hairpin folding transitions approximate two-state behavior.

Abstract-Eclampsia is considered a form of hypertensive encephalopathy in which an acute elevation in blood pressure causes autoregulatory breakthrough, blood-brain barrier disruption, and edema formation. We hypothesized that pregnancy predisposes the brain to eclampsia by lowering the pressure of autoregulatory breakthrough and enhancing cerebral edema formation. Because NO production is increased in pregnancy, we also investigated the role of NO in modulating autoregulation. Cerebral blood flow autoregulation was determined by phenylephrine infusion and laser Doppler flowmetry. Four groups were studied: untreated nonpregnant (nϭ7) and late-pregnant (days 19 to 21; nϭ8) Sprague-Dawley rats and nonpregnant (nϭ8) and late-pregnant (nϭ8) animals treated with an NO synthase inhibitor (N G -nitro-L-arginine methyl ester; 0.5 to 0.7 g/L). Brain water content and blood-brain barrier permeability to sodium fluorescein were determined after breakthrough. Pregnancy caused no change in autoregulation or the pressure of breakthrough. However, treatment with the NO synthase inhibitor significantly increased the pressure of autoregulatory breakthrough (nonpregnant: 183.6Ϯ3.0 mm Hg versus 212.0Ϯ2.8 mm Hg, PϽ0.05; late-pregnant: 180.8Ϯ3.2 mm Hg versus 209.3Ϯ4.7 mm Hg, PϽ0.05). After autoregulatory breakthrough, only late-pregnant animals showed a significant increase in cerebral edema formation, which was attenuated by NO synthase inhibition. There was no difference in blood-brain barrier permeability between nonpregnant and late-pregnant animals in response to acute hypertension, suggesting that pregnancy may predispose the brain to eclampsia by increasing cerebral edema through increased hydraulic conductivity. Key Words: autoregulation Ⅲ eclampsia Ⅲ L-NAME Ⅲ laser Doppler flowmetry Ⅲ NO synthase Ⅲ pregnancy E clampsia is a hypertensive disorder of pregnancy that occurs when hypertension in pregnancy presents with neurologic complications, including headache, nausea, vomiting, visual disturbances, and death. 1,2 This disease remains a leading cause of maternal and fetal mortality worldwide. [3][4][5] In fact, it is estimated that 40% of eclamptic deaths are due to cerebral involvement. 1 Eclampsia is thought to be a form of hypertensive encephalopathy. 6 -8 This acute syndrome occurs from a sudden and excessive elevation of blood pressure that causes forced dilatation of the cerebrovasculature, autoregulatory breakthrough, and hyperperfusion that leads to disruption of the blood-brain barrier (BBB) and vasogenic edema formation. 6,9,10 There is considerable evidence to suggest that eclampsia and hypertensive encephalopathy are similar, including similar symptoms (headache, nausea, vomiting, visual disturbances, and, in the most severe cases, convulsions) 2,6,9 and comparable findings on imaging that indicate white matter edema and evidence of localized BBB disruption. 6,11,12 In addition, clinical reports demonstrate increased cerebral blood flow (CBF) both before and after the onset of eclamptic seizures, 10,13-16 further...

Eclampsia is associated with increased blood-brain barrier (BBB) permeability and formation of cerebral oedema. Magnesium sulphate is used to treat eclampsia despite an unclear mechanism of action. This study was to determine the effect of magnesium sulphate on in vivo BBB permeability and formation of cerebral oedema during acute hypertension and on brain aquaporin-4 (AQP4) protein expression. An in vivo model of hypertensive encephalopathy was used in late-pregnant (LP) rats following magnesium sulphate treatment, 270 mg kg −1 I.P. injection every 4 h for 24 h. Permeability of the BBB was determined by in situ brain perfusion of Evan's Blue (EB) and sodium fluorescein (NaFl), and dye clearance determined by fluorescence spectrophotometry. Cerebral oedema was determined following acute hypertension by measuring brain water content. The effect of magnesium treatment on AQP4 expression was determined by Western blot analysis. Acute hypertension with autoregulatory breakthrough increased BBB permeability to EB in both brain regions studied (P < 0.05). Magnesium attenuated BBB permeability to EB during acute hypertension by 41% in the posterior cerebrum (P < 0.05) but had no effect in the anterior cerebrum (P > 0.05). Treatment with magnesium did not change NaFl permeability, cerebral oedema formation or AQP4 expression. In summary, BBB permeability to Evan's Blue was increased by acute hypertension in LP rats, and this was attenuated by treatment with magnesium sulphate. The greatest effect on BBB permeability to EB was in the posterior cerebrum, an area particularly susceptible to oedema formation during eclampsia.