title: HMGB1 Translocation After Ischemia in the Ovine Fetal Brain.
abstract: Inflammation contributes to the evolution of hypoxic-ischemic (HI) brain injury. High-mobility group box-1 (HMGB1) is a nuclear protein that is translocated from the nucleus and released after ischemia in adult rodents and thereby initiates inflammatory responses. However, there is very little information regarding the effects of HI on HMGB1 in immature brains. To investigate the effects of HI on HMGB1 in the term-equivalent fetal brain, ovine fetuses at 127 days gestation were studied after 30 minutes of carotid occlusion. Groups were sham-control and ischemia with 48 hours and ischemia with 72 hours of reperfusion. By immunohistochemistry, HMGB1 was found to be localized primarily in cell nuclei and partially in cytoplasmic compartments in the cerebral cortex of controls. Ischemia increased the area fraction of neuronal cells with cytoplasmic HMGB1 staining, and Western immunoblot revealed that cytosolic HMGB1 expression increased after ischemia (p < 0.05) and decreased in nuclei in ischemic versus the sham-control brains (p < 0.05). These data indicate that HMGB1 translocates from the nuclear to cytosolic compartments after ischemic brain injury in fetal sheep. This translocation may enable the action of HMGB1 as a proinflammatory cytokine that contributes to HI injury in the developing brain.
authors.affiliation: From the Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island (JZ, DK, KM, KA, BSS); Department of Physiology, University of Auckland, Auckland, New Zealand (JOD, GW, LB, AJG); Department of Pathology and Neurosurgery, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (EGS); and Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Okayama, Japan (KL, MN).
authors.forename: Jiyong
authors.initials: J
authors.lastname: Zhang
authors.affiliation: From the Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island (JZ, DK, KM, KA, BSS); Department of Physiology, University of Auckland, Auckland, New Zealand (JOD, GW, LB, AJG); Department of Pathology and Neurosurgery, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (EGS); and Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Okayama, Japan (KL, MN).
authors.forename: Daniel
authors.initials: D
authors.lastname: Klufas
authors.affiliation: From the Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island (JZ, DK, KM, KA, BSS); Department of Physiology, University of Auckland, Auckland, New Zealand (JOD, GW, LB, AJG); Department of Pathology and Neurosurgery, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (EGS); and Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Okayama, Japan (KL, MN).
authors.forename: Karina
authors.initials: K
authors.lastname: Manalo
authors.affiliation: From the Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island (JZ, DK, KM, KA, BSS); Department of Physiology, University of Auckland, Auckland, New Zealand (JOD, GW, LB, AJG); Department of Pathology and Neurosurgery, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (EGS); and Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Okayama, Japan (KL, MN).
authors.forename: Kwame
authors.initials: K
authors.lastname: Adjepong
authors.affiliation: From the Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island (JZ, DK, KM, KA, BSS); Department of Physiology, University of Auckland, Auckland, New Zealand (JOD, GW, LB, AJG); Department of Pathology and Neurosurgery, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (EGS); and Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Okayama, Japan (KL, MN).
authors.forename: Joanne O
authors.initials: JO
authors.lastname: Davidson
authors.affiliation: From the Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island (JZ, DK, KM, KA, BSS); Department of Physiology, University of Auckland, Auckland, New Zealand (JOD, GW, LB, AJG); Department of Pathology and Neurosurgery, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (EGS); and Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Okayama, Japan (KL, MN).
authors.forename: Guido
authors.initials: G
authors.lastname: Wassink
authors.affiliation: From the Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island (JZ, DK, KM, KA, BSS); Department of Physiology, University of Auckland, Auckland, New Zealand (JOD, GW, LB, AJG); Department of Pathology and Neurosurgery, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (EGS); and Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Okayama, Japan (KL, MN).
authors.forename: Laura
authors.initials: L
authors.lastname: Bennet
authors.affiliation: From the Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island (JZ, DK, KM, KA, BSS); Department of Physiology, University of Auckland, Auckland, New Zealand (JOD, GW, LB, AJG); Department of Pathology and Neurosurgery, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (EGS); and Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Okayama, Japan (KL, MN).
authors.forename: Alistair J
authors.initials: AJ
authors.lastname: Gunn
authors.affiliation: From the Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island (JZ, DK, KM, KA, BSS); Department of Physiology, University of Auckland, Auckland, New Zealand (JOD, GW, LB, AJG); Department of Pathology and Neurosurgery, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (EGS); and Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Okayama, Japan (KL, MN).
authors.forename: Edward G
authors.initials: EG
authors.lastname: Stopa
authors.affiliation: From the Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island (JZ, DK, KM, KA, BSS); Department of Physiology, University of Auckland, Auckland, New Zealand (JOD, GW, LB, AJG); Department of Pathology and Neurosurgery, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (EGS); and Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Okayama, Japan (KL, MN).
authors.forename: Keyue
authors.initials: K
authors.lastname: Liu
authors.affiliation: From the Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island (JZ, DK, KM, KA, BSS); Department of Physiology, University of Auckland, Auckland, New Zealand (JOD, GW, LB, AJG); Department of Pathology and Neurosurgery, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (EGS); and Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Okayama, Japan (KL, MN).
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nishibori
authors.affiliation: From the Department of Pediatrics, The Alpert Medical School of Brown University, Women & Infants Hospital of Rhode Island, Providence, Rhode Island (JZ, DK, KM, KA, BSS); Department of Physiology, University of Auckland, Auckland, New Zealand (JOD, GW, LB, AJG); Department of Pathology and Neurosurgery, The Alpert Medical School of Brown University, Rhode Island Hospital, Providence, Rhode Island (EGS); and Dentistry and Pharmaceutical Sciences, Graduate School of Medicine, Okayama University, Okayama, Japan (KL, MN). bstonestreet@wihri.org.
authors.forename: Barbara S
authors.initials: BS
authors.lastname: Stonestreet
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism / Q000473:pathology; D003593:Cytoplasm / Q000378:metabolism / Q000473:pathology; D005260:Female; D005333:Fetus / Q000378:metabolism / Q000473:pathology; D024243:HMGB1 Protein / Q000378:metabolism*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011897:Random Allocation; D012756:Sheep
chemical_list: D024243:HMGB1 Protein
keywords: Cytokine; Fetus; HMGB1; Inflammation; Ischemia; Sheep; Translocation.