BBB Injury and Neuroinflammation in Eclampsia

TOPLINE:

Eclampsia was associated with distinct cerebrospinal fluid (CSF) biomarker profiles, indicating severe disruption of the blood-brain barrier (BBB) and increased neuroinflammation.

METHODOLOGY:

• This investigation focused on BBB injury and neuroinflammation to elucidate mechanisms underlying cerebral injury.
• A total of 129 women from the Pre-eclampsia Obstetric Adverse Events biobank in South Africa who underwent caesarean delivery between March 2021 and June 2023 were included, of whom 11 had eclampsia, 17 had preeclampsia with end-organ complications, 88 had preeclampsia without end-organ complications, and 13 had normotensive pregnancies.
• An observational cross-sectional design was used; participants were stratified on the basis of the severity of preeclampsia (with end-organ complications).
• CSF and plasma samples were collected during spinal anaesthesia; CSF concentrations of claudin-5 and matrix metalloproteinase-9 and the CSF/plasma albumin ratio were measured; cytokine and chemokine levels were measured using the multiplex Bio-Plex assay.
• BBB injury markers and cytokine levels were compared using the analysis of covariance. Secondary outcomes included correlation analyses between CSF and plasma biomarkers.

TAKEAWAY:

• Women with eclampsia showed 2.7-fold higher claudin-5 concentrations in CSF than those with normotensive pregnancies (P = .005), with concentrations 4.0-fold higher than those with preeclampsia and end-organ complications and 3.1-fold higher than those with preeclampsia without end-organ complications.
• Interleukin (IL)-6 levels were significantly elevated (20.7-fold; P < .001); IL-8 (7.2-fold; P < .001) and IL-10 (2.0-fold; P = .004) levels were also increased.
• No correlation was observed between CSF and plasma cytokine levels (P > .05), but strong associations were noted between IL-6 and IL-8 levels (r = 0.74).
• Stem cell factor levels were significantly lower in women with eclampsia (0.5-fold decrease; P = .005) than in those with normotensive pregnancies; leukaemia inhibitory factor levels were 3.8-fold higher in those with eclampsia than in those with preeclampsia without end-organ complications.
• Monocyte chemoattractant protein-1 levels were 4.3-fold higher in women with eclampsia than in those with preeclampsia with end-organ complications; interferon-gamma levels were 2.9-fold higher in those with eclampsia than in those with preeclampsia and end-organ complications; IL-10 levels were 2.0-fold higher in those with eclampsia than in those with preeclampsia without end-organ complications.

IN PRACTICE:

“Women with eclampsia experience acute neuroinflammation and blood-brain barrier injury, comparable to patterns observed in neurodegenerative diseases such as acute traumatic brain injury, stroke or Alzheimer’s disease. Clinical follow-up of women with eclampsia postpartum should be considered,” the authors of the study wrote.

SOURCE:

This study was led by Valentina Bucher, PhD, Department of Obstetrics and Gynecology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. It was published online on May 08, 2025, in eBioMedicine.

LIMITATIONS:

This study was limited by the fact that samples were collected only after the onset of eclampsia, preventing the determination of whether BBB injury and neuroinflammation were causes or consequences of seizures. Despite having a substantial number of women with eclampsia, the small absolute number may have limited statistical power and introduced false-negative results.

DISCLOSURES:

This study was supported by the Swedish Research Council, Herbert och Karin Jacobssons Stiftelse, Wilhelm and Martina Lundgrens Foundations, and Swedish Society of Medicine. Some authors reported serving at scientific advisory boards and/or as consultants for several pharmaceutical organisations.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.