598: Assessment of blood-brain-barrier integrity and neuroinflammation in preeclampsia

Abstract

Circulating inflammatory factors may predispose to blood-brain-barrier impairment and neuroinflammation in preeclampsia, but human data is limited. We tested the hypothesis that peripheral inflammatory mediators (complement factors and cytokines) access cerebrospinal fluid (CSF) through a leaky blood-brain-barrier in preeclampsia. Prospective case-control study of pregnant women with a non-anomalous gestation >24 weeks, with indicated spinal anesthesia or combined spinal epidural analgesia. Women were enrolled in three groups: 1) Healthy controls; 2) Chronic or gestational hypertension and; 3) Preeclampsia with or without severe features. Blood and urine were collected before delivery, with CSF collected during spinal placement. In blood and CSF, we measured biomarkers using enzyme linked immunosorbent assays: albumin, C5a, C5b-9, TNF-α, and IL-6. Albumin and complement factors were also measured in urine. The CSF/plasma albumin quotient was used to assess blood-brain-barrier integrity. Clinical data was abstracted from the medical record. Differences were assessed by ANOVA, chi-squared test, or test of medians, with α=0.05. In total, 48 subjects enrolled (16 per arm) and summary characteristics are detailed in Table 1. Plasma, urine and CSF measurements for albumin, C5a, C5b-9, TNF-α, and IL-6 are shown in Table 2. Preeclampsia was associated with increased plasma levels of terminal complement effector C5b-9 (membrane attack complex) and pro- inflammatory cytokine IL-6. Marked urinary excretion of C5b-9 in preeclampsia (p<0.001) confirmed end-organ effects in the kidney. Despite systemic complement activation and end-organ injury in preeclampsia, C5b-9 remained undetectable in CSF. Levels of IL-6 were detectable in CSF, but they did not increase in conjunction with rising plasma levels in preeclampsia. Likewise, albumin was detectable in CSF, but the CSF/plasma albumin quotient did not increase in preeclampsia (p=0.78, vs. controls). Moreover, CSF albumin levels were not increased in the subset of 8 preeclampsia subjects with severe features [median 16.0 mg/dl, interquartile range (12.5-17.0)]. We find that the integrity of the blood-brain-barrier is maintained in preeclampsia despite evidence of systemic inflammation and terminal complement activation.View Large Image Figure ViewerDownload Hi-res image Download (PPT)