High-mobility group box-1 translocation and release after hypoxic ischemic brain injury in neonatal rats

Xiaodi Chen, Jiyong Zhang, Boram Kim, Siddhant Jaitpal, Steven S. Meng, Kwame Adjepong, Sayumi Imamura, Hidenori Wake, Masahiro Nishibori, Edward G. Stopa, Barbara S. Stonestreet

Research output: Contribution to journalArticle

Abstract

Inflammation contributes to neonatal brain injury. Pro-inflammatory cytokines represent key inflammatory meditators in neonatal hypoxic-ischemic (HI) brain injury. The high mobility group box-1 (HMGB1) protein is a nuclear protein with pro-inflammatory cytokine properties when it is translocated from the nucleus and released extracellularly after stroke in adult rodents. We have previously shown that HMGB1 is translocated from the nucleus to cytosolic compartment after ischemic brain injury in fetal sheep. In the current study, we utilized the Rice-Vannucci model to investigate the time course of HMGB1 translocation and release after HI injury in neonatal rats. HMGB1 was located in cellular nuclei of brains from sham control rats. Nuclear to cytoplasmic translocation of HMGB1 was detected in the ipsilateral-HI hemisphere as early as zero h after HI, and released extracellularly as early as 6 h after HI. Immunohistochemical double staining detected HMGB1 translocation mainly in neurons along with release from apoptotic cells after HI. Serum HMGB1 increased at 3 h and decreased by 24 h after HI. In addition, rat brains exposed to hypoxic injury alone also exhibited time dependent HMGB1 translocation at 3, 12 and 48 h after hypoxia. Consequently, HMGB1 responds similarly after HI injury in the brains of neonatal and adult subjects. We conclude that HMGB1 is sensitive early indicator of neonatal HI and hypoxic brain injury.

LanguageEnglish
Pages1-14
Number of pages14
JournalExperimental Neurology
Volume311
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

Brain Injuries
Cytokines
HMGB1 Protein
Wounds and Injuries
Brain
Nuclear Proteins
Rodentia
Sheep
Stroke
Staining and Labeling
Inflammation
Neurons
Serum

Keywords

  • Brain
  • HMGB1
  • Hypoxia
  • Ischemia
  • Neonate

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Chen, X., Zhang, J., Kim, B., Jaitpal, S., Meng, S. S., Adjepong, K., ... Stonestreet, B. S. (2019). High-mobility group box-1 translocation and release after hypoxic ischemic brain injury in neonatal rats. Experimental Neurology, 311, 1-14. https://doi.org/10.1016/j.expneurol.2018.09.007

High-mobility group box-1 translocation and release after hypoxic ischemic brain injury in neonatal rats. / Chen, Xiaodi; Zhang, Jiyong; Kim, Boram; Jaitpal, Siddhant; Meng, Steven S.; Adjepong, Kwame; Imamura, Sayumi; Wake, Hidenori; Nishibori, Masahiro; Stopa, Edward G.; Stonestreet, Barbara S.

In: Experimental Neurology, Vol. 311, 01.01.2019, p. 1-14.

Research output: Contribution to journalArticle

Chen, X, Zhang, J, Kim, B, Jaitpal, S, Meng, SS, Adjepong, K, Imamura, S, Wake, H, Nishibori, M, Stopa, EG & Stonestreet, BS 2019, 'High-mobility group box-1 translocation and release after hypoxic ischemic brain injury in neonatal rats' Experimental Neurology, vol. 311, pp. 1-14. https://doi.org/10.1016/j.expneurol.2018.09.007
Chen, Xiaodi ; Zhang, Jiyong ; Kim, Boram ; Jaitpal, Siddhant ; Meng, Steven S. ; Adjepong, Kwame ; Imamura, Sayumi ; Wake, Hidenori ; Nishibori, Masahiro ; Stopa, Edward G. ; Stonestreet, Barbara S. / High-mobility group box-1 translocation and release after hypoxic ischemic brain injury in neonatal rats. In: Experimental Neurology. 2019 ; Vol. 311. pp. 1-14.
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