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Updated: Apr 18, 2026
Instrumentation of Near-term Fetal Sheep for Multivariate Chronic Non-anesthetized Recordings
Published on: October 25, 2015
Anti-IL-6 neutralizing antibody modulates blood-brain barrier function in the ovine fetus
Jiyong Zhang1, Grazyna B Sadowska1, Xiaodi Chen1
1*Department of Pediatrics, Alpert Medical School of Brown University, Women and Infants Hospital of Rhode Island, Providence, Rhode Island, USA; ProThera Biologics, Incorporated, Providence, Rhode Island, USA; Department of Electrical, Computer, and Biomedical Engineering, University of Rhode Island, Kingston, Rhode Island, USA; Department of Neurology, Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island, USA; and Geriatric Research Educational, and Clinical Center, Veterans Affairs Puget Sound Health Care System, Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, Washington, USA.
Abstract:
Impaired blood-brain barrier function represents an important component of hypoxic-ischemic brain injury in the perinatal period. Proinflammatory cytokines could contribute to ischemia-related blood-brain barrier dysfunction. IL-6 increases vascular endothelial cell monolayer permeability in vitro. However, contributions of IL-6 to blood-brain barrier abnormalities have not been examined in the immature brain in vivo. We generated pharmacologic quantities of ovine-specific neutralizing anti-IL-6 mAbs and systemically infused mAbs into fetal sheep at 126 days of gestation after exposure to brain ischemia. Anti-IL-6 mAbs were measured by ELISA in fetal plasma, cerebral cortex, and cerebrospinal fluid, blood-brain barrier permeability was quantified using the blood-to-brain transfer constant in brain regions, and IL-6, tight junction proteins, and plasmalemma vesicle protein (PLVAP) were detected by Western immunoblot. Anti-IL-6 mAb infusions resulted in increases in mAb (P < 0.05) in plasma, brain parenchyma, and cerebrospinal fluid and decreases in brain IL-6 protein. Twenty-four hours after ischemia, anti-IL-6 mAb infusions attenuated ischemia-related increases in blood-brain barrier permeability and modulated tight junction and PLVAP protein expression in fetal brain. We conclude that inhibiting the effects of IL-6 protein with systemic infusions of neutralizing antibodies attenuates ischemia-related increases in blood-brain barrier permeability by inhibiting IL-6 and modulates tight junction proteins after ischemia.
