Anti–High Mobility Group Box 1 Antibody Therapy May Prevent Cognitive Dysfunction After Traumatic Brain Injury

Yu Okuma, Hidenori Wake, Kiyoshi Teshigawara, Yu Takahashi, Tomohito Hishikawa, Takao Yasuhara, Shuji Mori, Hideo K. Takahashi, Isao Date, Masahiro Nishibori

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Background: High mobility group box 1 (HMGB1) protein plays a key role in triggering inflammatory responses in many diseases. Our previous study showed that HMGB1 is found upstream of secondary damage in traumatic brain injury (TBI). We found that anti-HMGB1 monoclonal antibody (mAb) effectively decreased acute brain damage, including the disruption of the blood-brain barrier, brain edema, and neurologic dysfunction. This effect of anti-HMGB1 mAb lasts for at least 1 week. In this study, we explored subacute effects of anti-HMGB1 mAb after TBI. Methods: TBI was induced in rats by fluid percussion. Anti-HMGB1 mAb or control mAb was given intravenously after TBI. Histochemical staining, plasma levels of HMGB1, motor activity and memory, and video electroencephalography monitoring were evaluated 2 weeks after fluid percussion injury. Results: Anti-HMGB1 mAb remarkably attenuated accumulation of activated microglia in the rat cortex in the ipsilateral hemisphere after TBI. Anti-HMGB1 mAb also prevented neuronal death in the hippocampus in the ipsilateral hemisphere after TBI. Treatment of rats with anti-HMGB1 mAb inhibited HMGB1 translocation and suppressed impairment of motor function. The beneficial effects of anti-HMGB1 mAb on motor and cognitive function persisted for 14 days after injury. Treatment with anti-HMGB1 mAb also had positive effects on electroencephalography activity. Conclusions: The beneficial effects of anti-HMGB1 mAb continued during the subacute postinjury phase, suggesting that anti-HMGB1 mAb may prevent cognitive dysfunction after TBI.

Original languageEnglish
JournalWorld Neurosurgery
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Monoclonal Antibodies
Antibodies
Therapeutics
Percussion
Traumatic Brain Injury
Cognitive Dysfunction
Electroencephalography
HMGB1 Protein
Brain Edema
Wounds and Injuries
Microglia
Neurologic Manifestations
Blood-Brain Barrier
Cognition
Hippocampus
Motor Activity
Staining and Labeling
Brain

Keywords

  • Cognitive dysfunction
  • Electroencephalography
  • High mobility group box 1
  • Traumatic brain injury

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

Cite this

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title = "Anti–High Mobility Group Box 1 Antibody Therapy May Prevent Cognitive Dysfunction After Traumatic Brain Injury",
abstract = "Background: High mobility group box 1 (HMGB1) protein plays a key role in triggering inflammatory responses in many diseases. Our previous study showed that HMGB1 is found upstream of secondary damage in traumatic brain injury (TBI). We found that anti-HMGB1 monoclonal antibody (mAb) effectively decreased acute brain damage, including the disruption of the blood-brain barrier, brain edema, and neurologic dysfunction. This effect of anti-HMGB1 mAb lasts for at least 1 week. In this study, we explored subacute effects of anti-HMGB1 mAb after TBI. Methods: TBI was induced in rats by fluid percussion. Anti-HMGB1 mAb or control mAb was given intravenously after TBI. Histochemical staining, plasma levels of HMGB1, motor activity and memory, and video electroencephalography monitoring were evaluated 2 weeks after fluid percussion injury. Results: Anti-HMGB1 mAb remarkably attenuated accumulation of activated microglia in the rat cortex in the ipsilateral hemisphere after TBI. Anti-HMGB1 mAb also prevented neuronal death in the hippocampus in the ipsilateral hemisphere after TBI. Treatment of rats with anti-HMGB1 mAb inhibited HMGB1 translocation and suppressed impairment of motor function. The beneficial effects of anti-HMGB1 mAb on motor and cognitive function persisted for 14 days after injury. Treatment with anti-HMGB1 mAb also had positive effects on electroencephalography activity. Conclusions: The beneficial effects of anti-HMGB1 mAb continued during the subacute postinjury phase, suggesting that anti-HMGB1 mAb may prevent cognitive dysfunction after TBI.",
keywords = "Cognitive dysfunction, Electroencephalography, High mobility group box 1, Traumatic brain injury",
author = "Yu Okuma and Hidenori Wake and Kiyoshi Teshigawara and Yu Takahashi and Tomohito Hishikawa and Takao Yasuhara and Shuji Mori and Takahashi, {Hideo K.} and Isao Date and Masahiro Nishibori",
year = "2018",
month = "1",
day = "1",
doi = "10.1016/j.wneu.2018.10.164",
language = "English",
journal = "World Neurosurgery",
issn = "1878-8750",
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T1 - Anti–High Mobility Group Box 1 Antibody Therapy May Prevent Cognitive Dysfunction After Traumatic Brain Injury

AU - Okuma, Yu

AU - Wake, Hidenori

AU - Teshigawara, Kiyoshi

AU - Takahashi, Yu

AU - Hishikawa, Tomohito

AU - Yasuhara, Takao

AU - Mori, Shuji

AU - Takahashi, Hideo K.

AU - Date, Isao

AU - Nishibori, Masahiro

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Background: High mobility group box 1 (HMGB1) protein plays a key role in triggering inflammatory responses in many diseases. Our previous study showed that HMGB1 is found upstream of secondary damage in traumatic brain injury (TBI). We found that anti-HMGB1 monoclonal antibody (mAb) effectively decreased acute brain damage, including the disruption of the blood-brain barrier, brain edema, and neurologic dysfunction. This effect of anti-HMGB1 mAb lasts for at least 1 week. In this study, we explored subacute effects of anti-HMGB1 mAb after TBI. Methods: TBI was induced in rats by fluid percussion. Anti-HMGB1 mAb or control mAb was given intravenously after TBI. Histochemical staining, plasma levels of HMGB1, motor activity and memory, and video electroencephalography monitoring were evaluated 2 weeks after fluid percussion injury. Results: Anti-HMGB1 mAb remarkably attenuated accumulation of activated microglia in the rat cortex in the ipsilateral hemisphere after TBI. Anti-HMGB1 mAb also prevented neuronal death in the hippocampus in the ipsilateral hemisphere after TBI. Treatment of rats with anti-HMGB1 mAb inhibited HMGB1 translocation and suppressed impairment of motor function. The beneficial effects of anti-HMGB1 mAb on motor and cognitive function persisted for 14 days after injury. Treatment with anti-HMGB1 mAb also had positive effects on electroencephalography activity. Conclusions: The beneficial effects of anti-HMGB1 mAb continued during the subacute postinjury phase, suggesting that anti-HMGB1 mAb may prevent cognitive dysfunction after TBI.

AB - Background: High mobility group box 1 (HMGB1) protein plays a key role in triggering inflammatory responses in many diseases. Our previous study showed that HMGB1 is found upstream of secondary damage in traumatic brain injury (TBI). We found that anti-HMGB1 monoclonal antibody (mAb) effectively decreased acute brain damage, including the disruption of the blood-brain barrier, brain edema, and neurologic dysfunction. This effect of anti-HMGB1 mAb lasts for at least 1 week. In this study, we explored subacute effects of anti-HMGB1 mAb after TBI. Methods: TBI was induced in rats by fluid percussion. Anti-HMGB1 mAb or control mAb was given intravenously after TBI. Histochemical staining, plasma levels of HMGB1, motor activity and memory, and video electroencephalography monitoring were evaluated 2 weeks after fluid percussion injury. Results: Anti-HMGB1 mAb remarkably attenuated accumulation of activated microglia in the rat cortex in the ipsilateral hemisphere after TBI. Anti-HMGB1 mAb also prevented neuronal death in the hippocampus in the ipsilateral hemisphere after TBI. Treatment of rats with anti-HMGB1 mAb inhibited HMGB1 translocation and suppressed impairment of motor function. The beneficial effects of anti-HMGB1 mAb on motor and cognitive function persisted for 14 days after injury. Treatment with anti-HMGB1 mAb also had positive effects on electroencephalography activity. Conclusions: The beneficial effects of anti-HMGB1 mAb continued during the subacute postinjury phase, suggesting that anti-HMGB1 mAb may prevent cognitive dysfunction after TBI.

KW - Cognitive dysfunction

KW - Electroencephalography

KW - High mobility group box 1

KW - Traumatic brain injury

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