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Tumor Necrosis Factor induces cerebral edema and increased cerebrovascular permeability in normal pregnant rats
Author(s) -
Warrington Junie Paula,
Ryan Michael J,
Drummond Heather A,
Spradley Frank T,
Granger Joey P
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.907.9
Subject(s) - medicine , evans blue , extravasation , preeclampsia , cerebral edema , endocrinology , tumor necrosis factor alpha , edema , vascular permeability , ischemia , blood–brain barrier , anesthesia , pathology , pregnancy , central nervous system , biology , genetics
Cerebrovascular events contribute to ~40% of preeclampsia/eclampsia deaths and preeclamptic patients commonly present with neurological symptoms. Our laboratory recently showed that placental ischemia, induced by reducing uterine perfusion pressure, closely mimics preeclamptic patients resulting in cerebral edema and increased inflammatory cytokines such as tumor necrosis factor (TNFα). In this study, we examined whether TNFα, infused via intraperitoneal implanted mini‐osmotic pumps (100ng/day from gestational day 14 to 19), contributes to cerebral edema and blood‐brain barrier (BBB) disruption in normal pregnant rats. Mean arterial pressure, measured via carotid catheters, was significantly increased in TNFα infused rats (112 vs. 107 mmHg; p=0.01). Brain water content, calculated as (wet weight ‐ dry weight)/ wet weight × 100, was also significantly increased in TNFα infused rats (78.2 vs. 77.9%; p=0.01). BBB permeability, assayed using the Evans blue extravasation method, was increased in the hippocampus of TNFα‐infused rats (p<0.05) but was unchanged in the striatum, cerebellum, and anterior brain. Our results indicate that TNFα released from ischemic placentas, could mediate cerebral edema through increased BBB permeability. TNFα may be an important clinical target for preventing cerebrovascular complications associated with preeclampsia. Funding: NIH Grant HL108618