HMGB1 translocation after ischemia in the ovine fetal brain

Jiyong Zhang, Daniel Klufas, Karina Manalo, Kwame Adjepong, Joanne O. Davidson, Guido Wassink, Laura Bennet, Alistair J. Gunn, Edward G. Stopa, Keyue Liu, Masahiro Nishibori, Barbara S. Stonestreet

Research output: Contribution to journalArticle

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)527-538
Number of pages12
JournalJournal of Neuropathology and Experimental Neurology
Volume75
Issue number6
DOIs
Publication statusPublished - Jun 1 2016

Fingerprint

Sheep
Ischemia
Brain
Brain Injuries
Nuclear Proteins
Cell Nucleus
Cerebral Cortex
Reperfusion
Rodentia
Fetus
Western Blotting
Immunohistochemistry
Staining and Labeling
Cytokines
Inflammation
Pregnancy
Wounds and Injuries

Keywords

  • Cytokine
  • Fetus
  • HMGB1
  • Inflammation
  • Ischemia
  • Sheep
  • Translocation

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medicine(all)
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Zhang, J., Klufas, D., Manalo, K., Adjepong, K., Davidson, J. O., Wassink, G., ... Stonestreet, B. S. (2016). HMGB1 translocation after ischemia in the ovine fetal brain. Journal of Neuropathology and Experimental Neurology, 75(6), 527-538. https://doi.org/10.1093/jnen/nlw030

HMGB1 translocation after ischemia in the ovine fetal brain. / Zhang, Jiyong; Klufas, Daniel; Manalo, Karina; Adjepong, Kwame; Davidson, Joanne O.; Wassink, Guido; Bennet, Laura; Gunn, Alistair J.; Stopa, Edward G.; Liu, Keyue; Nishibori, Masahiro; Stonestreet, Barbara S.

In: Journal of Neuropathology and Experimental Neurology, Vol. 75, No. 6, 01.06.2016, p. 527-538.

Research output: Contribution to journalArticle

Zhang, J, Klufas, D, Manalo, K, Adjepong, K, Davidson, JO, Wassink, G, Bennet, L, Gunn, AJ, Stopa, EG, Liu, K, Nishibori, M & Stonestreet, BS 2016, 'HMGB1 translocation after ischemia in the ovine fetal brain', Journal of Neuropathology and Experimental Neurology, vol. 75, no. 6, pp. 527-538. https://doi.org/10.1093/jnen/nlw030
Zhang J, Klufas D, Manalo K, Adjepong K, Davidson JO, Wassink G et al. HMGB1 translocation after ischemia in the ovine fetal brain. Journal of Neuropathology and Experimental Neurology. 2016 Jun 1;75(6):527-538. https://doi.org/10.1093/jnen/nlw030
Zhang, Jiyong ; Klufas, Daniel ; Manalo, Karina ; Adjepong, Kwame ; Davidson, Joanne O. ; Wassink, Guido ; Bennet, Laura ; Gunn, Alistair J. ; Stopa, Edward G. ; Liu, Keyue ; Nishibori, Masahiro ; Stonestreet, Barbara S. / HMGB1 translocation after ischemia in the ovine fetal brain. In: Journal of Neuropathology and Experimental Neurology. 2016 ; Vol. 75, No. 6. pp. 527-538.
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