Plasma From Patients With HELLP Syndrome Increases Blood—Brain Barrier Permeability

Abstract

Circulating inflammatory factors and endothelial dysfunction have been proposed to contribute to the pathophysiology of hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome. To date, the occurrence of neurological complications in these women has been reported, but few studies have examined whether impairment in blood-brain barrier (BBB) permeability or cerebrovascular reactivity is present in women having HELLP syndrome. We hypothesized that plasma from women with HELLP syndrome causes increased BBB permeability and cerebrovascular dysfunction. Posterior cerebral arteries from female nonpregnant rats were perfused with 20% serum from women with normal pregnancies (n ¼ 5) or women with HELLP syndrome (n ¼ 5), and BBB permeability and vascular reactivity were compared. Plasma from women with HELLP syndrome increased BBB permeability while not changing myogenic tone and reactivity to pressure. Addition of the nitric oxide (NO) synthase inhibitor N o -nitro-L-arginine methyl ester caused constriction of arteries that was not different with the different plasmas nor was dilation to the NO donor sodium nitroprusside different between the 2 groups. However, dilation to the smalland intermediate-conductance, calcium-activated potassium channel activator NS309 was decreased in vessels exposed to HELLP plasma. Thus, increased BBB permeability in response to HELLP plasma was associated with selective endothelial dysfunction.

Mechanisms and outcomes of stroke during pregnancy and the postpartum period

“…22 In a follow-up study, the authors noted that when plasma from women with HELLP syndrome was infused into the posterior cerebral arteries of rats it caused increased blood-brain barrier permeability and diminished vasodilation in response to calcium-activated potassium channels. 23 In our group, 33% of the pregnancy-related RCVS cases had coexisting preeclampsia; none were documented as having HELLP syndrome. The finding that a history of migraine appeared to increase the odds of pregnancy-associated RCVS is intriguing.…”

Inhibition of T‐cell activation attenuates hypertension, TNFα, IL‐17, and blood–brain barrier permeability in pregnant rats with angiogenic imbalance

“…Similar to PE, women with HELLP syndrome have evidence of systemic inflammation 20, 21 and most recently we have reported that plasma collected from women with HELLP syndrome is capable of increasing BBB permeability compared to plasma from women with a normal pregnancy 7 . These finding suggest that plasma from women with HELLP syndrome contains certain factors that potentially contribute to BBB disruption.…”

“…Women with HELLP syndrome can also develop a variety of neurologically related maternal morbidities which include cerebral hemorrhage, blurred vision and cognitive impairments during gestation and in the immediate post-partum period 4–6 . We recently reported that plasma from women with HELLP syndrome significantly increased blood brain barrier (BBB) permeability, which suggests that factors in the circulation are capable of impairing the BBB 7 .…”

Peripheral Anti-Angiogenic Imbalance during Pregnancy Impairs Myogenic Tone and Increases Cerebral Edema in a Rodent Model of HELLP Syndrome

“…HELLP syndrome is associated with changes in systemic inflammation, as characterized by immune system dysfunction, endothelial dysfunction, and angiogenic imbalance [8]. The systemic inflammatory changes that occur in HELLP syndrome may also play a role in the CNS abnormalities seen in women with HELLP syndrome, and may possibly contribute to the long-term vascular damage that has been reported in women with HELLP syndrome and severe preeclampsia [2,9,10,11]. We have previously reported that plasma from women with HELLP syndrome leads to impairment in the blood brain barrier (BBB), suggesting that yet undefined variables in the circulation system are contributing to the damage.…”

“…To study these mechanisms, we infused anti-angiogenic factors soluble fms like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng) into pregnant rats to create an animal model of HELLP syndrome [10,12]. Similar to what is reported in women with HELLP syndrome [13,14], animals with HELLP have evidence of increased inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin-17 (IL-17), and cytokine releasing CD4 + and CD8 + T cells [15].…”