Cerebral Biomarkers and Blood-Brain Barrier Integrity in Preeclampsia

Abstract

Cerebral complications in preeclampsia contribute substantially to maternal mortality and morbidity. There is a lack of reliable and accessible predictors for preeclampsia-related cerebral complications. In this study, plasma from women with preeclampsia (n = 28), women with normal pregnancies (n = 28) and non-pregnant women (n = 16) was analyzed for concentrations of the cerebral biomarkers neurofilament light (NfL), tau, neuron-specific enolase (NSE) and S100B. Then, an in vitro blood–brain barrier (BBB) model, based on the human cerebral microvascular endothelial cell line (hCMEC/D3), was employed to assess the effect of plasma from the three study groups. Transendothelial electrical resistance (TEER) was used as an estimation of BBB integrity. NfL and tau are proteins expressed in axons, NSE in neurons and S100B in glial cells and are used as biomarkers for neurological injury in other diseases such as dementia, traumatic brain injury and hypoxic brain injury. Plasma concentrations of NfL, tau, NSE and S100B were all higher in women with preeclampsia compared with women with normal pregnancies (8.85 vs. 5.25 ng/L, p < 0.001; 2.90 vs. 2.40 ng/L, p < 0.05; 3.50 vs. 2.37 µg/L, p < 0.001 and 0.08 vs. 0.05 µg/L, p < 0.01, respectively). Plasma concentrations of NfL were also higher in women with preeclampsia compared with non-pregnant women (p < 0.001). Higher plasma concentrations of the cerebral biomarker NfL were associated with decreased TEER (p = 0.002) in an in vitro model of the BBB, a finding which indicates that NfL could be a promising biomarker for BBB alterations in preeclampsia.

Preeclampsia history and postpartum risk of cerebrovascular disease and cognitive impairment: Potential mechanisms

“…Other studies that have assessed markers of neuronal injury or neuroinflammation in women with preeclampsia or eclampsia during pregnancy have shown increased pro-inflammatory cytokines in cerebrospinal fluid from preeclampsia and eclampsia patients compared to normal pregnant women (Bergman et al, 2021b). Increased plasma concentration of different markers of glial or neuronal damage were found in women with preeclampsia compared to normal pregnant women (Friis et al, 2022). Taken together, clinical and preclinical studies demonstrate increased BBB permeability in preeclampsia with evidence of involvement of extracellular vesicles, pro-inflammatory cytokines, and other factors during pregnancy.…”

Preeclampsia and its relationship to pathological brain aging

“…Cerebral biomarkers for neurological injury in dementia include neurofilament light and tau found in axons, as well as neuron-specific enolase and S100B found in glial cells ( Friis et al, 2022 ). Recent studies investigated whether these cerebral biomarkers for neurological injury were present in cases of preeclampsia and the findings were inconsistent.…”

“…The existing literature is not entirely consistent, however. Friis et al ( Friis et al, 2022 ) reported increased plasma concentrations of neurofilament light, tau, neuron-specific enolase, and S100B in women with preeclampsia compared to women who had normative pregnancies. Conflicting findings such as those related to S100B highlight the need for additional research regarding the underlying influences of cerebral biomarkers.…”

“…Cerebral biomarkers were associated with blood-brain barrier integrity. Higher concentrations of neurofilament light chain were associated with decreased transendothelial electrical resistance, indicating damage to the blood-brain barrier ( Friis et al, 2022 ). Additional evidence suggested the blood-brain barrier may be injured in both preeclampsia and eclampsia.…”

Brain Vascular Dysfunction in Mothers and Their Children Exposed to Preeclampsia

“…This finding indicates that NfL could be a promising biomarker for BBB alterations in preeclampsia. 111…”