214. TNFα impairs cerebral blood flow autoregulation during pregnancy

Abstract

Background Cerebral complications are a leading cause of morbidity and mortality in preeclamptic pregnancies, accounting for approximately 40% of all preeclampsia/eclampsia related deaths. However, the underlying pathophysiological mechanisms remain unclear. Given the central role of the ischemic placenta in driving preeclampsia, we hypothesized that circulating factors released from the ischemic placenta directly impair cerebral vascular function and blood brain barrier permeability. Specifically, the role of TNFα, an inflammatory cytokine increased in the placenta and circulation of preeclamptic pregnancies, was examined. Methods Pregnant Sprague Dawley Rats were infused with vehicle or TNFα (200 ng/day i.p, from gestational day 14 to 19). Evan’s blue extravasation was measured in the cerebral cortex as an indicator of blood brain barrier (BBB) permeability, and brain water content was assessed as an indicator of cerebral edema at the time of euthanasia. In a separate experimental group, rats were infused with vehicle or TNFα in order to examine the impact on cerebral blood flow (CBF) autoregulation during pregnancy. CBF was measured by laser Doppler flowmetry under anesthesia. Rats were intubated and ventilated in order to maintain constant blood gases, and mean arterial pressure was elevated step-wise from 100-190 mmHg by infusion of phenylephrine to determine changes in CBF. Results Infusion of TNFα in pregnant rats caused a significant 10 mmHg increase in arterial pressure (n = 12, p Conclusions These data suggest that increasing TNFα to levels observed during preeclampsia results in cerebral vascular changes that may mechanistically underlie the increased risk for encephalopathy.