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

8 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
Pages (from-to)e864-e871
JournalWorld Neurosurgery
Volume122
DOIs
Publication statusPublished - Feb 2019

Keywords

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

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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