91-OR]: New biomarkers in cerebrospinal fluid for cerebrovascular involvement in preeclampsia

Severe preeclampsia presents as a multi-organ disorder, affecting the liver, kidney, brain, and clotting system. In the brain, this sometimes leads to complications, such as eclamptic seizures and stroke. A disturbed autoregulatory response of the brain to blood pressure changes and endothelial cell dysfunction may be causative factors. Currently, no clinically useful biomarker is available to investigate the integrity of the blood-brain barrier in preeclamptic patients. Our objective was to identify new biomarkers in cerebrospinal fluid for cerebrovascular involvement in preeclampsia.A case-control study was conducted among preeclamptic and normotensive pregnant women undergoing a caesarean section or a cervical cerclage procedure. During spinal anesthesia, 1mL of cerebrospinal fluid was collected. The samples were analyzed using a nano-LC-Orbitrap mass spectrometer.Cerebrospinal fluid samples of 43 pre-eclamptic patients and 55 normotensive controls were obtained. Free hemoglobin was identified in the cerebrospinal fluid of patients and controls. Eight proteins were upregulated and 17 were downregulated in women with preeclampsia. The alpha-1-microglobulin/bikunin precursor was the most distinctive protein we identified. This protein is a precursor of a heme-binding protein that counteracts the damaging effects of free hemoglobin.We identified new potential biomarkers for cerebral involvement in preeclampsia. The presence of free hemoglobin in the cerebrospinal fluid of patients and controls is quite remarkable, when compared with cerebrospinal fluid of nonpregnant subjects. This could possibly be explained by a modulated blood-brain barrier permeability during pregnancy. This suggests that pregnancy makes the brain more vulnerable to hypertension-related brain complications. Whether this finding is a key to cerebrovascular involvement in preeclampsia needs to be further elucidated.C.B. van den Berg: None. J.J. Duvekot: None. C. Güzel: None. T.G. de Leeuw: None. T.M. Luider: None. E.A. Steegers: None. H. Versendaal: None. M.P. Stoop: None.