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

doi:10.1016/j.expneurol.2018.09.007

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 journal › Article › peer-review

29 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1-14
Number of pages	14
Journal	Experimental Neurology
Volume	311
DOIs	https://doi.org/10.1016/j.expneurol.2018.09.007
Publication status	Published - Jan 2019

Keywords

Brain
HMGB1
Hypoxia
Ischemia
Neonate

ASJC Scopus subject areas

Neurology
Developmental Neuroscience

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10.1016/j.expneurol.2018.09.007

Cite this

@article{c7235ef5932f4ace855988434c891438,

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

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.",

keywords = "Brain, HMGB1, Hypoxia, Ischemia, Neonate",

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

note = "Funding Information: Research reported in this publication was supported by the American Heart Association Postdoctoral Fellowship Award: 13POST16860015 , National Institute of General Medical Sciences of the National Institutes of Health under award numbers 1R01-HD-057100 , R21-NS096525 , an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20 RR018728 and P20GM103537 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2019",

month = jan,

doi = "10.1016/j.expneurol.2018.09.007",

language = "English",

volume = "311",

pages = "1--14",

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T1 - High-mobility group box-1 translocation and release after hypoxic ischemic brain injury in neonatal rats

AU - Chen, Xiaodi

AU - Zhang, Jiyong

AU - Kim, Boram

AU - Jaitpal, Siddhant

AU - Meng, Steven S.

AU - Adjepong, Kwame

AU - Imamura, Sayumi

AU - Wake, Hidenori

AU - Nishibori, Masahiro

AU - Stopa, Edward G.

AU - Stonestreet, Barbara S.

N1 - Funding Information: Research reported in this publication was supported by the American Heart Association Postdoctoral Fellowship Award: 13POST16860015 , National Institute of General Medical Sciences of the National Institutes of Health under award numbers 1R01-HD-057100 , R21-NS096525 , an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20 RR018728 and P20GM103537 . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: © 2018 Elsevier Inc.

PY - 2019/1

Y1 - 2019/1

N2 - 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.

AB - 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.

KW - Brain

KW - HMGB1

KW - Hypoxia

KW - Ischemia

KW - Neonate

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JO - Experimental Neurology

JF - Experimental Neurology

ER -

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

Abstract

Keywords

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