Age-dependent release of high-mobility group box protein-1 and cellular neuroinflammation after traumatic brain injury in mice

Research output: Contribution to journalArticleResearchpeer-review

2 Citations (Scopus)

Abstract

Accumulating research suggests that children may be more vulnerable to poor long-term outcomes after traumatic brain injury (TBI) compared to adults. The neuroinflammatory response, known to contribute to neuropathology after TBI, appears to differ depending upon age-at-insult, although this response has not been well-characterized. Elevated levels of a key initiator of inflammation, high-mobility group box protein 1 (HMGB1), have been associated with worsened outcomes after TBI in young patients. This study therefore aimed to characterize the acute time course of key mediators of the inflammatory cascade, including HMGB1, after pediatric and adult TBI. Male C57Bl/6 mice were subjected to severe controlled cortical impact or a sham control surgery, at either early adulthood (8–10 weeks) or a pediatric age (3 weeks). Cortical tissue was collected for Western blot detection of astrocyte and microglial activation (GFAP and CD68) and HMGB1 at 2 hr, 6 hr, 24 hr, 3 days, and 7 days postinjury, and serum was collected for enzyme-linked immunoassays to quantify peripheral HMGB1. An additional cohort of brains was harvested at 3 day postinjury for immunofluorescence staining. Results demonstrated a temporal profile of CD68, GFAP, and HMGB1 after TBI relative to sham, which differed between the adult and pediatric cohorts. An increase in peripheral HMGB1 was found in serum from pediatric TBI mice, which was not evident in adult serum. Together, these findings demonstrate that HMGB1 and the downstream cellular inflammatory response are influenced by age-at-insult, which may be an important consideration for treatment strategies aiming to ameliorate this response after TBI.

Original languageEnglish
Pages (from-to)1102-1117
Number of pages16
JournalJournal of Comparative Neurology
Volume527
Issue number6
DOIs
Publication statusPublished - 15 Apr 2019

Keywords

  • age
  • high mobility group box protein 1
  • inflammation
  • pediatric
  • RRID:AB_10013382
  • RRID:AB_10679369
  • RRID:AB_11212597
  • RRID:AB_1141557
  • RRID:AB_141607
  • RRID:AB_141637
  • RRID:AB_2224402
  • RRID:AB_2298772
  • RRID:AB_2305186
  • RRID:AB_2534105
  • RRID:AB_2617143
  • RRID:AB_444360
  • RRID:AB_783595
  • traumatic brain injury

Cite this

@article{46dba18e563a4fba826ac609f6a6ee73,
title = "Age-dependent release of high-mobility group box protein-1 and cellular neuroinflammation after traumatic brain injury in mice",
abstract = "Accumulating research suggests that children may be more vulnerable to poor long-term outcomes after traumatic brain injury (TBI) compared to adults. The neuroinflammatory response, known to contribute to neuropathology after TBI, appears to differ depending upon age-at-insult, although this response has not been well-characterized. Elevated levels of a key initiator of inflammation, high-mobility group box protein 1 (HMGB1), have been associated with worsened outcomes after TBI in young patients. This study therefore aimed to characterize the acute time course of key mediators of the inflammatory cascade, including HMGB1, after pediatric and adult TBI. Male C57Bl/6 mice were subjected to severe controlled cortical impact or a sham control surgery, at either early adulthood (8–10 weeks) or a pediatric age (3 weeks). Cortical tissue was collected for Western blot detection of astrocyte and microglial activation (GFAP and CD68) and HMGB1 at 2 hr, 6 hr, 24 hr, 3 days, and 7 days postinjury, and serum was collected for enzyme-linked immunoassays to quantify peripheral HMGB1. An additional cohort of brains was harvested at 3 day postinjury for immunofluorescence staining. Results demonstrated a temporal profile of CD68, GFAP, and HMGB1 after TBI relative to sham, which differed between the adult and pediatric cohorts. An increase in peripheral HMGB1 was found in serum from pediatric TBI mice, which was not evident in adult serum. Together, these findings demonstrate that HMGB1 and the downstream cellular inflammatory response are influenced by age-at-insult, which may be an important consideration for treatment strategies aiming to ameliorate this response after TBI.",
keywords = "age, high mobility group box protein 1, inflammation, pediatric, RRID:AB_10013382, RRID:AB_10679369, RRID:AB_11212597, RRID:AB_1141557, RRID:AB_141607, RRID:AB_141637, RRID:AB_2224402, RRID:AB_2298772, RRID:AB_2305186, RRID:AB_2534105, RRID:AB_2617143, RRID:AB_444360, RRID:AB_783595, traumatic brain injury",
author = "Webster, {Kyria M.} and Mujun Sun and Crack, {Peter J.} and O'Brien, {Terence J.} and Shultz, {Sandy R.} and Semple, {Bridgette D.}",
year = "2019",
month = "4",
day = "15",
doi = "10.1002/cne.24589",
language = "English",
volume = "527",
pages = "1102--1117",
journal = "Journal of Comparative Neurology",
issn = "0021-9967",
publisher = "Wiley-Blackwell",
number = "6",

}

Age-dependent release of high-mobility group box protein-1 and cellular neuroinflammation after traumatic brain injury in mice. / Webster, Kyria M.; Sun, Mujun; Crack, Peter J.; O'Brien, Terence J.; Shultz, Sandy R.; Semple, Bridgette D.

In: Journal of Comparative Neurology, Vol. 527, No. 6, 15.04.2019, p. 1102-1117.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Age-dependent release of high-mobility group box protein-1 and cellular neuroinflammation after traumatic brain injury in mice

AU - Webster, Kyria M.

AU - Sun, Mujun

AU - Crack, Peter J.

AU - O'Brien, Terence J.

AU - Shultz, Sandy R.

AU - Semple, Bridgette D.

PY - 2019/4/15

Y1 - 2019/4/15

N2 - Accumulating research suggests that children may be more vulnerable to poor long-term outcomes after traumatic brain injury (TBI) compared to adults. The neuroinflammatory response, known to contribute to neuropathology after TBI, appears to differ depending upon age-at-insult, although this response has not been well-characterized. Elevated levels of a key initiator of inflammation, high-mobility group box protein 1 (HMGB1), have been associated with worsened outcomes after TBI in young patients. This study therefore aimed to characterize the acute time course of key mediators of the inflammatory cascade, including HMGB1, after pediatric and adult TBI. Male C57Bl/6 mice were subjected to severe controlled cortical impact or a sham control surgery, at either early adulthood (8–10 weeks) or a pediatric age (3 weeks). Cortical tissue was collected for Western blot detection of astrocyte and microglial activation (GFAP and CD68) and HMGB1 at 2 hr, 6 hr, 24 hr, 3 days, and 7 days postinjury, and serum was collected for enzyme-linked immunoassays to quantify peripheral HMGB1. An additional cohort of brains was harvested at 3 day postinjury for immunofluorescence staining. Results demonstrated a temporal profile of CD68, GFAP, and HMGB1 after TBI relative to sham, which differed between the adult and pediatric cohorts. An increase in peripheral HMGB1 was found in serum from pediatric TBI mice, which was not evident in adult serum. Together, these findings demonstrate that HMGB1 and the downstream cellular inflammatory response are influenced by age-at-insult, which may be an important consideration for treatment strategies aiming to ameliorate this response after TBI.

AB - Accumulating research suggests that children may be more vulnerable to poor long-term outcomes after traumatic brain injury (TBI) compared to adults. The neuroinflammatory response, known to contribute to neuropathology after TBI, appears to differ depending upon age-at-insult, although this response has not been well-characterized. Elevated levels of a key initiator of inflammation, high-mobility group box protein 1 (HMGB1), have been associated with worsened outcomes after TBI in young patients. This study therefore aimed to characterize the acute time course of key mediators of the inflammatory cascade, including HMGB1, after pediatric and adult TBI. Male C57Bl/6 mice were subjected to severe controlled cortical impact or a sham control surgery, at either early adulthood (8–10 weeks) or a pediatric age (3 weeks). Cortical tissue was collected for Western blot detection of astrocyte and microglial activation (GFAP and CD68) and HMGB1 at 2 hr, 6 hr, 24 hr, 3 days, and 7 days postinjury, and serum was collected for enzyme-linked immunoassays to quantify peripheral HMGB1. An additional cohort of brains was harvested at 3 day postinjury for immunofluorescence staining. Results demonstrated a temporal profile of CD68, GFAP, and HMGB1 after TBI relative to sham, which differed between the adult and pediatric cohorts. An increase in peripheral HMGB1 was found in serum from pediatric TBI mice, which was not evident in adult serum. Together, these findings demonstrate that HMGB1 and the downstream cellular inflammatory response are influenced by age-at-insult, which may be an important consideration for treatment strategies aiming to ameliorate this response after TBI.

KW - age

KW - high mobility group box protein 1

KW - inflammation

KW - pediatric

KW - RRID:AB_10013382

KW - RRID:AB_10679369

KW - RRID:AB_11212597

KW - RRID:AB_1141557

KW - RRID:AB_141607

KW - RRID:AB_141637

KW - RRID:AB_2224402

KW - RRID:AB_2298772

KW - RRID:AB_2305186

KW - RRID:AB_2534105

KW - RRID:AB_2617143

KW - RRID:AB_444360

KW - RRID:AB_783595

KW - traumatic brain injury

UR - http://www.scopus.com/inward/record.url?scp=85059257425&partnerID=8YFLogxK

U2 - 10.1002/cne.24589

DO - 10.1002/cne.24589

M3 - Article

VL - 527

SP - 1102

EP - 1117

JO - Journal of Comparative Neurology

JF - Journal of Comparative Neurology

SN - 0021-9967

IS - 6

ER -