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Circulating tumor necrosis factor-\u03b1 (TNF-\u03b1) is elevated in preeclamptic women, and infusion of TNF-\u03b1 into pregnant rats mimics characteristics of preeclampsia. While this suggests that TNF-\u03b1 has a mechanistic role to promote preeclampsia, the impact of TNF-\u03b1 on the cerebral vasculature during pregnancy remains unclear. We tested the hypothesis that TNF-\u03b1 contributes to cerebrovascular abnormalities during placental ischemia by first infusing TNF-\u03b1 in pregnant rats (200 ng\/day ip, from gestational day 14 to 19) at levels to mimic those reported in preeclamptic women. TNF-\u03b1 increased mean arterial pressure (MAP, P &lt; 0.05) and brain water content in the anterior cerebrum ( P &lt; 0.05); however, TNF-\u03b1 infusion had no effect on blood-brain barrier (BBB) permeability in the anterior cerebrum or posterior cerebrum. We then assessed the role of endogenous TNF-\u03b1 in mediating these abnormalities in a model of placental ischemia induced by reducing uterine perfusion pressure followed by treatment with the soluble TNF-\u03b1 receptor (etanercept, 0.8 mg\/kg sc) on gestational day 18. Etanercept reduced placental ischemia-mediated increases in MAP, anterior brain water content ( P &lt; 0.05), and BBB permeability (202 \u00b1 44% in placental ischemic rats to 101 \u00b1 28% of normal pregnant rats). Our results indicate that TNF-\u03b1 mechanistically contributes to cerebral edema by increasing BBB permeability and is an underlying factor in the development of cerebrovascular abnormalities associated with preeclampsia complicated by placental ischemia.<\/jats:p>","DOI":"10.1152\/ajpregu.00372.2015","type":"journal-article","created":{"date-parts":[[2015,9,23]],"date-time":"2015-09-23T22:37:50Z","timestamp":1443047870000},"page":"R1425-R1431","source":"Crossref","is-referenced-by-count":58,"title":["Placental ischemia-induced increases in brain water content and cerebrovascular permeability: role of TNF-\u03b1"],"prefix":"10.1152","volume":"309","author":[{"given":"Junie P.","family":"Warrington","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heather 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