Evidence of Neuroinflammation and Blood-Brain Barrier Disruption in Women with Preeclampsia and Eclampsia.

Cerebral complications in preeclampsia are leading causes of maternal mortality. Animal models suggest that an injured blood-brain barrier and neuroinflammation may be important but there is paucity of data from human studies. Therefore, we aimed to evaluate this in women with preeclampsia and eclampsia. We included women recruited to the South African Preeclampsia Obstetric Adverse Events (PROVE) biobank. Blood and cerebrospinal fluid (CSF) were collected around delivery. CSF was analyzed for neuroinflammatory markers interleukin 1ß, interleukin 6, interleukin-8 and tumor necrosis factor alpha (TNF-alpha). The CSF to plasma albumin ratio was measured to assess blood-brain barrier function. Women with eclampsia (n = 4) showed increased CSF concentrations of all pro-inflammatory cytokines and TNF-alpha compared to women with normotensive pregnancies (n = 7) and also for interleukin-6 and TNF-alpha compared to women with preeclampsia (n = 4). Women with preeclampsia also showed increases in pro-inflammatory cytokines IL-6 and IL-8 but not TNF-alpha in the CSF compared to women with normotensive pregnancies. In particular, women with eclampsia but also women with preeclampsia showed an increase in the CSF to plasma albumin ratio compared to normotensive women. In conclusion, women with preeclampsia and eclampsia show evidence of neuroinflammation and an injured blood-brain barrier. These findings are seen in particular among women with eclampsia.

Signs of neuroaxonal injury in preeclampsia-A case control study.

BACKGROUND: Cerebral injury is a common cause of maternal mortality due to preeclampsia and is challenging to predict and diagnose. In addition, there are associations between previous preeclampsia and stroke, dementia and epilepsy later in life. The cerebral biomarkers S100B, neuron specific enolase, (NSE), tau protein and neurofilament light chain (NfL) have proven useful as predictors and diagnostic tools in other neurological disorders. This case-control study sought to determine whether cerebral biomarkers were increased in cerebrospinal fluid (CSF) as a marker of cerebral origin and potential cerebral injury in preeclampsia and if concentrations in CSF correlated to concentrations in plasma. METHODS: CSF and blood at delivery from 15 women with preeclampsia and 15 women with normal pregnancies were analysed for the cerebral biomarkers S100B, NSE, tau protein and NfL by Simoa and ELISA based methods. MRI brain was performed after delivery and for women with preeclampsia also at six months postpartum. RESULTS: Women with preeclampsia demonstrated increased CSF- and plasma concentrations of NfL and these concentrations correlated to each other. CSF concentrations of NSE and tau were decreased in preeclampsia and there were no differences in plasma concentrations of NSE and tau between groups. For S100B, serum concentrations in preeclampsia were increased but there was no difference in CSF concentrations of S100B between women with preeclampsia and normal pregnancy. CONCLUSION: NfL emerges as a promising circulating cerebral biomarker in preeclampsia and increased CSF concentrations point to a neuroaxonal injury in preeclampsia, even in the absence of clinically evident neurological complications.

Cerebrospinal beta-amyloid peptides(1-40) and (1-42) in severe preeclampsia and HELLP syndrome - a pilot study.

During pregnancy, substantial alterations in cerebral plasticity, vascular remodeling and neuronal growth occur in the maternal brain. We investigated whether concentrations of selected neurodiagnostic biomarkers in the cerebrospinal fluid of women with preeclampsia/HELLP syndrome differ from those in healthy controls using enzyme-linked immunosorbent assay technique. We found that tau protein concentrations (p = 0.016) and phospho-tau/tau ratio (p < 0.001) in cerebrospinal fluid were significantly lower in 39 preeclamptic women compared to 44 healthy controls during third trimester of pregnancy. Beta-amyloid(1-40)/(1-42) ratio was significantly higher in HELLP syndrome than in severe preeclampsia (8.49 + 2.73 vs. 4.71 + 1.65; p = 0.007). We conclude that beta-amyloid(1-40)/(1-42) ratio in cerebrospinal fluid can discriminate severe preeclampsia and HELLP syndrome. High beta-amyloid peptide and low tau protein concentrations are associated with impaired development of the materno-feto-placental unit and correlate with placental dysfunction.

New highly sensitive sandwich ELISA system for soluble endoglin quantification in different biological fluids.

Soluble endoglin (sEng) is a fragment of a membrane-associated receptor (CD105) expressed on endothelial cells, mesenchymal stem cells and trophoblast cells. It is considered as a regulatory factor involved in the development of preeclampsia (PE) and cancer-associated neo-angiogenesis. The purpose of this study was to describe a new sandwich ELISA for sEng quantification. In contrast to three commercial kits, the new ELISA was able to quantify sEng not only in blood plasma and cell culture supernatants, but also in urine and cerebrospinal fluid. The assay detected up to two orders of magnitude higher antigen levels than did the commercial kits. Using Western blot assay followed by SDS-PAGE or Blue Native PAGE, we demonstrated a heterogeneous nature of sEng molecules. Antigen heterogeneity is considered as a factor contributing to the pronounced differences in its content estimations by different ELISAs. We obtained evidence indicating that the assay was capable of detecting heterogenious sEng molecules. The new ELISA was validated as a quick, specific and accurate method for sEng quantification. Despite the differences in antigen content estimates, the assay had similar diagnostic performance as widely used commercial kit for the detection of severe PE in pregnant women based on plasma sEng contents. Moreover, the new assay was able to delineate diseased patients based on antigen levels in urine. Therefore, the new ELISA is a potentially valuable tool for in vitro and clinical studies.

Cerebrospinal Fluid Protein Changes in Preeclampsia.

The molecular mechanisms underlying seizure susceptibility in preeclampsia are unknown. We hypothesized that altered expression of distinct proteins in the cerebrospinal fluid (CSF) may reflect pathophysiological changes in the central nervous system that contribute to the neurological manifestations of severe preeclampsia. We obtained CSF samples from 13 patients with preeclampsia and 14 control patients during spinal anesthesia before delivery and analyzed them by SOMAscan, an aptamer-based proteomics platform for alterations in 1310 protein levels. Ingenuity Pathway Analysis was conducted to highlight relationships between preeclampsia-specific proteins found to be significantly altered. For 2 of the target proteins, we validated the difference in CSF concentrations by ELISA. SOMAscan revealed 82 proteins, whose expression levels were significantly different (P<0.05) in CSF from patients with preeclampsia versus controls. Principal component analysis achieved perfect separation of the preeclampsia and control groups in 2 dimensions. The differentially expressed proteins converge around 4 signaling molecules: TGF-ß (transforming growth factor-ß), VEGFA (vascular endothelial growth factor A), angiotensinogen, and IL-6 (interleukin-6). Within the TGF-ß pathway, upregulation of activin A (301.6±47.4 versus 151.6±20.5 pg/mL; P=0.0074) and follistatin-related gene (5129±347 versus 3016±188 pg/mL; P<0.0001) in preeclampsia was confirmed by ELISA. In summary, signaling pathways important for vascular remodeling, inflammation, and neuronal growth, signaling, and electrophysiology were well represented among the proteins found to be altered in CSF in patients with preeclampsia.

Cerebrospinal fluid levels of tau and phospho-tau-181 proteins during pregnancy.

OBJECTIVES: During pregnancy various interactions occur between structural alterations of the maternal brain and placental metabolism. The aim of the present study was to investigate whether cerebrospinal fluid concentrations of tau and phospho-tau-181 protein vary during normal pregnancy and in women with preeclampsia and HELLP syndrome. STUDY DESIGN: We measured cerebrospinal fluid biomarkers, tau and phospho-tau-181 protein levels in 90 pregnant women electively assigned for regional anaesthesia during pregnancy or for cesarean section using enzyme-linked immunosorbent assays. RESULTS: Cerebrospinal fluid concentrations for tau and phospho-tau-181 in 66 women with normal pregnancy were 308.5±117.3pg/mL and 50.5±16.7pg/mL, respectively. Blood pressure, liver function, clotting activity and kidney function were significantly different in eleven women with preeclampsia and HELLP syndrome. The weight of the newly born (p<0.001; HR: 0.998), the weight of the placenta (p=0.018) and concentrations for phospho-tau-181 (p=0.043; HR: 1.211) correlated significantly with the disease. CONCLUSION: Mean concentrations of cerebrospinal fluid tau and phospho-tau-181 protein during pregnancy were evaluated. Phospho-tau-181 protein concentrations correlated with placental function supporting the hypothesis that altered expression of neuronal factors during pregnancy may affect development of the placenta.

[BLOOD AND CEREBROSPINAL FLUID PURINES IN PREGNANT].

The research includes 88 pregnant women, that had their purine basis and malondialdehyde in water thermocoagulate extract of venous blood and cerebrospinal fluid examined (along with common standards clinical-laboratory tests) before the spinal anesthesia for the caesarian section was provided It was detected that preeclampsy and HELLP-syndine feature the increased adenine guanine hypoxantine and uric acid levels in cerebrospinal fluid, as well as increased concentrations of blood malondyaldehyde (higher than upper normal level), accompany with the increased hemotaencephalic barrier permeability for adenine, guanine and hypoxantine. It's demonstrated that level of guanine in blood serum can be used as a prognostic factor of spinal anesthesia quality in obstetrics. It is supposed to examine purine levels in pregnant women not only in blood but also in cere brospinal fluid.

Cerebral spinal fluid and serum ionized magnesium and calcium levels in preeclamptic women during administration of magnesium sulfate.

OBJECTIVE: To study the distribution of ionized and total magnesium (Mg) in serum and cerebral spinal fluid (CSF) in preeclamptic women receiving MgSO(4) and how this treatment affects the ionized calcium (Ca(2+)) and ionized Ca:Mg ratios compared with healthy nonpregnant women and pregnant control women (HP). DESIGN: Controlled clinical study. SETTING: An academic medical center. PATIENT(S): African-American women older than 20 and less than 35 years. The pregnant preeclamptic study and pregnant control groups each consisted of 16 women; the nonpregnant group consisted of 10 subjects. INTERVENTION(S): The preeclamptic women received a 6-g bolus of MgSO(4) IV started at least 4.5 hours before delivery during 15-20 minutes, then 2 g/h baseline. MAIN OUTCOME MEASURE(S): The CSF and serum levels of Ca(2+) and Mg(2+) and total Mg were measured in all three groups of women. The Ca(2+):Mg(2+) ratios were determined. Physiologic monitoring was done and recorded every 4 hours where appropriate. Bloods were drawn every 6 hours for complete blood count, metabolic panel, lactate dehydrogenase, uric acid, and electrolytes. Serum pH, total Mg, Apgar scores, and general health of the infants born to preeclamptic mothers given MgSO(4) were followed. RESULT(S): The HP showed a reduction in mean serum ionized and total Mg, increase in ionized Ca, and a large increase in Ca(2+):Mg(2+) ratios compared with healthy nonpregnant women. Although the CSF ionized and total Mg and Ca(2+):Mg(2+) ratios were not altered with MgSO(4) treatment in the preeclamptic women receiving MgSO(4), the mean serum Mg values increased 3-fold. All infants were full-term, regardless of MgSO(4) treatment, and normal with respect to birth weight, Apgar scores, blood pH, total Mg, and neurologic scores. CONCLUSION(S): The data indicate that there is a direct relationship between the serum and CSF Ca(2+):Mg(2+) ratios in HP and this ratio may be crucial in preventing vascular and neurologic complications in preeclampsia-eclampsia.

Placental growth factor in the cerebrospinal fluid of women with preeclampsia.

OBJECTIVE: Recent data suggest that excess circulating soluble fms-like tyrosine kinase-1 (sFlt-1) may causally relate to preeclampsia. This study investigates the levels of sFlt-1, VEGF, and PlGF in cerebrospinal fluid (CSF) of patients with preeclampsia and normotensive controls. METHODS: CSF was collected from preeclamptic patients (n=15) and controls (n=7) at the time of spinal anesthesia and assayed for PlGF, sFlt-1, and VEGF (total and free) by specific immunoassays. RESULTS: All sought angiogenic factors were measurable. Levels of free PlGF but not sFlt-1 or VEGF (total or free) were increased in CSF of preeclamptic women. There was no significant difference in the ratios of angiogenic factors in the CSF of women with preeclampsia. There was no correlation between levels of angiogenic factors and CSF cell counts or severity of symptoms. CONCLUSION: Elevated levels of PlGF in CSF preeclamptic women may promote vascular permeability and contribute to the hypertensive encephalopathy seen in such patients.

Discriminatory proteomic biomarker analysis identifies free hemoglobin in the cerebrospinal fluid of women with severe preeclampsia.

OBJECTIVE: Preeclampsia is an idiopathic multisystem disorder specific to human pregnancy. This study used proteomic analysis of cerebrospinal fluid (CSF) to identify protein biomarkers characteristic of preeclampsia and related to its severity. STUDY DESIGN: CSF was collected from women diagnosed clinically with severe preeclampsia (sPE: n = 7), mild preeclampsia (mPE: n = 8), and normotensive controls (CRL: n = 8). Samples were subjected to proteomic analysis using surface-enhanced laser desorption/ionization time-of-flight (SELDI-TOF) mass spectroscopy. A discriminative proteomic biomarker profile was extracted by applying Mass Restricted analysis, and a Preeclampsia Proteomic Biomarker (PPB) score developed based on the presence or absence of four discriminatory protein peaks in individual CSF SELDI tracings. In-gel tryptic digests, Western blot analysis, on-chip immunoassays, ELISA, and spectral analysis were used to identify the biomarkers composing the PPB score. RESULTS: PPB score distinguished patients with a clinical diagnosis of sPE from mPE and CRLs. (PPB median [range]: sPE: 4 [0-4] vs mPE: 1 [0-1] vs CRL: 0 [0-0]; P < 0.001). PPB scores were unaffected by parity, magnesium seizure prophylaxis, CSF leukocyte counts, and total protein content. Proteomic identification techniques matched the discriminatory protein peaks to the alpha- and beta-hemoglobin chains. ELISA confirmed that women diagnosed clinically with sPE had significantly higher CSF hemoglobin concentrations than women with mPE or CRL (median [range]: sPE: 6.6 [0.0-10.3] microg/mL vs mPE: 0 [0-1.3] microg/mL vs CRL: 0 [0-0] microg/mL; P < 0.001). CONCLUSION: Proteomic analysis of CSF can accurately distinguish sPE from both mPE and CRL. Patients with sPE have nanomolar amounts of free hemoglobin in their CSF. Further studies are needed to confirm these observations and determine their physiologic implications.

Effects of pre-eclampsia on maternal plasma, cerebrospinal fluid, and umbilical cord urotensin II concentrations: a pilot study.

BACKGROUND: Urotensin II (UII) is the most potent endogenous vasoconstrictor identified to date. Pre-eclampsia is associated with arteriolar vasospasm but the precise underlying mechanism is uncertain and we hypothesized that UII concentrations might also be elevated. In this study we measured UII concentrations in maternal plasma and cerebrospinal fluid (CSF), and umbilical vein plasma from pre-eclamptic (PET) and normotensive patients undergoing elective Caesarean section under spinal or combined spinal-epidural anaesthesia. METHODS: With LREC approval and informed consent we recruited two groups of 10 patients; control [mean (range) age, 29 (22-43) yr; BMI, 25 (20-32); gestation, 273 (267-281) days; mean arterial pressure (MAP) on day of delivery, 81 (75-96) mm Hg] and PET [age, 34 (22-40) yr; BMI, 25 (21-46); gestation, 253 (203-289) days; MAP on day of delivery, 106 (88-128) mm Hg]. Maternal blood and CSF samples and umbilical vein blood samples were taken. UII was extracted and concentrations measured using a radioimmunoassay. RESULTS: Two plasma and two CSF samples in the control and two CSF samples in the PET group were below the assay detection limits. There were no differences in maternal plasma or CSF or umbilical vein UII concentrations between the groups. However, there was a small ( approximately 40%) but significant increase in cord UII concentrations when compared with paired plasma in the PET group. There was a weak but significant negative correlation (r=-0.4, P=0.049) between cord UII concentrations and gestation in the PET group. In addition, we observed a significant positive correlation between plasma and CSF (r(2)=+0.57, P=0.0009, n=16), plasma and cord (r(2)=+0.43, P=0.0031, n=18) and CSF and cord (r(2)=+0.32, P=0.022, n=16) UII concentrations for the whole data set. CONCLUSIONS: Collectively the data indicate that UII concentrations do not increase in PET compared with controls but, in PET patients, cord UII concentrations are elevated relative to paired plasma samples. Elevated umbilical vein UII concentrations may simply indicate reduced placental viability and possibly UII metabolism as a result of reduced blood flow or possibly that the placenta is producing UII.

Cerebrospinal fluid leptin levels in preeclampsia: relation to maternal serum leptin levels.

BACKGROUND: To determine whether cerebrospinal fluid (CSF) and circulating levels of leptin differ between women with preeclampsia and women who had an uncomplicated pregnancy. METHODS: Maternal serum and CSF leptin concentrations obtained in the third trimester of the gestation were compared in 16 women with mild preeclampsia and 23 normotensive pregnant women who underwent cesarean section. Before administering local anesthetic for spinal anesthesia, 2 mL CSF and 4 mL venous blood sample were taken and were stored at -30 degrees C until serum and CSF leptin levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Mean CSF leptin concentrations were not significantly different between the two groups (preeclampsia 9.7 +/- 4.2 ng/mL, normotensive 13.6 +/- 4.3 ng/mL, p = 0.952). Similarly, mean serum leptin concentrations were similar between the two groups (mild preeclampsia 21.7 +/- 7.1 ng/mL, normotensive 18.3 +/- 6.7 ng/mL, p = 0.698). CSF leptin levels are inversely related to the serum leptin concentrations in preeclamptic patients (r = -0.87, p = 0.000). An inverse relationship was also detected between CSF and serum leptin levels in normotensive pregnant subjects (r = -0.66, p = 0.000). CONCLUSIONS: CSF and serum leptin levels were similar in patients with preeclampsia and normotensive pregnant women. However, the CSF leptin was negatively correlated with the serum leptin concentrations in preeclamptic and normotensive control subjects, suggesting that leptin enters the brain by a saturable transport system. Further work is needed to confirm our findings.

Cerebrospinal fluid nitric oxide level changes in preeclampsia.

OBJECTIVE: The purpose of this study was to determine the level of nitric oxide (NO) metabolites, nitrite and nitrate in human cerebrospinal fluid (CSF) and serum and to assess whether there is any relationship among CSF, serum nitrate-nitrite levels and preeclampsia. STUDY DESIGN: Twenty-one preeclamptic and 27 healthy pregnant women as control group who underwent cesarean section (C/S) were included in the study. Before administering local anesthetic for spinal anesthesia, 2 ml CSF and 4 ml venous blood sample were taken. CSF and serum total nitrite, direct nitrite and nitrate levels were determined spectrophotometrically. RESULTS: CSF total nitrite, direct nitrite and nitrate levels were significantly different between the two groups (21.00+/-1.68, 8.28+/-0.89 and 12.71+/-1.08 micromol/l, respectively versus 15.53+/-1.49, 5.57+/-0.39 and 9.96+/-1.45 micromol/l, respectively, P<0.05). Significantly higher serum nitrate level was found (31.84+/-2.31 micromol/l) in the control group compared to the preeclamptic group serum nitrate level (25.06+/-2.02 micromol/l). Statistical comparisons were performed by the Mann-Whitney U-test. CONCLUSION: CSF-NO is significantly higher but serum NO is lower in preeclamptic group compared with control group may suggest independent regulation of NO in the two compartments. The determination of CSF-NO metabolites could be useful to clarify whether increased NO production is predominantly associated with poor perfusion of the brain in preeclampsia.

Baseline serum and cerebrospinal fluid magnesium levels in normal pregnancy and preeclampsia.

OBJECTIVE: To determine whether baseline cerebrospinal fluid magnesium levels in preeclampsia differ from those in normal pregnancy, and to ascertain whether pre-treatment cerebrospinal fluid magnesium levels correlate with serum levels, which would suggest a baseline alteration in the blood-brain barrier in preeclampsia. METHODS: When spinal analgesia or anesthesia was administered for delivery, serum and cerebrospinal fluid magnesium levels were determined in 20 normal gravidas and 20 preeclamptic women not treated with magnesium sulfate. Data were analyzed by two-sided Student t test and regression analysis. RESULTS: Mean (+/- standard deviation) cerebrospinal fluid magnesium level for preeclamptic patients was 2.23 +/- 0.09 mEq/L, which was not significantly different from controls. Regression analysis revealed no significant correlation between cerebrospinal fluid and serum magnesium levels for either normal or preeclamptic gravidas. CONCLUSION: During the third trimester, there is no difference in baseline, pre-treatment cerebrospinal fluid magnesium levels in preeclamptic patients compared to normal subjects, and no correlation between cerebrospinal fluid and serum magnesium over the range of baseline values.

Cerebrospinal fluid and plasma glucose concentrations of ovine pregnancy toxaemia cases, inappetant ewes and normal ewes during late gestation.

Cerebrospinal fluid (CSF) and plasma glucose concentrations of spontaneous ovine pregnancy toxaemia cases, determined within 24 h of the onset of clinical signs, were significantly lower (P < 0.01) compared to inappetant ewes and healthy ewes at a similar stage of gestation. A highly significant correlation (P < 0.001, r = 0.91) was present between the plasma and CSF glucose concentrations when the data from the three groups were combined. The data suggest that plasma glucose concentration accurately reflects CSF glucose concentration across the range of energy states in pregnant ewes and may provide support for the postulate that the neurological signs of ovine pregnancy toxaemia result from cerebral hypoglycaemia, as reflected by CSF glucose concentration. No cerebral glucose estimations were undertaken in this series.

The total peroxyl radical-trapping ability of plasma and cerebrospinal fluid in normal and preeclamptic parturients.

Plasma and cerebrospinal fluid total peroxyl radical-trapping antioxidative parameter (TRAP) and the main antioxidant components of TRAP (vitamin E, ascorbic acid, uric acid, protein sulfhydryl groups, and the unidentified antioxidant proportion) were analyzed in 11 preeclamptic parturients, 9 healthy parturients with an uncomplicated pregnancy, and 10 healthy nonpregnant women. In addition, the possible effects of ongoing labor were studied in 10 healthy parturients. The samples of plasma and cerebrospinal fluid (CSF) were collected at cesarean section (pregnant women) or minor surgical procedure (nonpregnant women). Normal pregnancy or ongoing labor induced no significant changes in total TRAP, as compared with nonpregnant women, but significant changes in the percentage contributions of individual antioxidants were noted in plasma and CSF. In preeclampsia, a significant increase in TRAP was noted in both plasma and CSF. This increase was mainly due to an increased proportion of uric acid and unidentified antioxidants in plasma samples, and an increased proportion of unidentified antioxidants in CSF. The concentration of CSF ascorbic acid was decreased in preeclampsia, and a negative correlation between CSF ascorbic acid and blood pressure was observed.

Catecholamine concentrations in venous plasma and cerebrospinal fluid in normal and complicated pregnancy.

The concentrations of adrenaline and noradrenaline were determined in venous plasma and cerebrospinal fluid (CSF) of 41 pregnant women at term scheduled for elective or 'hot' caesarean section and in 7 healthy non-pregnant women scheduled for elective surgery. Group 1: 10 pregnant women at term with a normal history of their pregnancy; group 2: like group 1, but in active labour for more than 4 h; group 3: 10 pregnant women with insulin-dependent diabetes mellitus with or without slightly elevated arterial blood pressure; group 4: 11 women with pre-eclampsia gravis; group 5: 7 healthy non-pregnant women of fertile age. The highest values of mean arterial blood pressure and of venous plasma noradrenaline were found in the pre-eclamptic group 4, mean arterial blood pressure and plasma noradrenaline levels correlated to each other. However, concentrations of noradrenaline in CSF in group 4 did not differ significantly from the other groups. It is speculated that a different origin of hypertension may be the reason for the normal noradrenaline concentrations in CSF. This finding is in contrast to earlier findings in which noradrenaline levels in CSF were elevated in patients with essential hypertension.

Cerebrospinal fluid levels of magnesium in patients with preeclampsia after treatment with intravenous magnesium sulfate: a preliminary report.

The purpose of this study is twofold: (1) to correlate magnesium levels of serum with those of cerebrospinal fluid in patients with preeclampsia receiving intravenous magnesium sulfate, and (2) to determine whether the magnesium ion crosses the blood-brain barrier in significant amounts after intravenous magnesium sulfate therapy. Of the 21 patients in whom spinal anesthesia was used for delivery, ten patients with preeclampsia with therapeutic serum magnesium levels made up the study group and 11 term nontreated normotensive gravid women served as controls. At the time of spinal anesthesia, a 1 ml aliquot of cerebrospinal fluid was obtained from each patient. The mean cerebrospinal fluid magnesium level for the control group was 2.56 +/- 0.19 mg/dl (range 2.2 to 2.8 mg/dl). For the preeclamptic group who received intravenous magnesium sulfate, the mean cerebrospinal fluid magnesium level was 3.04 +/- 0.12 mg/dl (range 2.9 to 3.2 mg/dl). Although only a small amount of magnesium crosses the blood-brain barrier after intravenous magnesium sulfate treatment, this increment is highly significant (p less than 0.001).