• Yu Okuma, Hidenori Wake, Kiyoshi Teshigawara, Yu Takahashi, Tomohito Hishikawa, Takao Yasuhara, Shuji Mori, Hideo K Takahashi, Isao Date, and Masahiro Nishibori.
• Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Okayama, Japan; Department of Neurological Surgery, Okayama University Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Okayama, Japan; Department of Neurological Surgery, Hiroshima City Hiroshima Citizens Hospital, Hiroshima, Japan.
• World Neurosurg. 2019 Feb 1; 122: e864-e871.

BackgroundHigh 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.MethodsTBI 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.ResultsAnti-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.ConclusionsThe beneficial effects of anti-HMGB1 mAb continued during the subacute postinjury phase, suggesting that anti-HMGB1 mAb may prevent cognitive dysfunction after TBI.Copyright © 2018 Elsevier Inc. All rights reserved.

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