Program

PO1-1-44

Anti-High Mobility Group Box-1 Antibody Therapy Might Prevent Cognitive Dysfunction After Traumatic Brain Injury

[Speaker] Yu Okuma:1
[Co-author] Keyue Liu:2, Hidenori Wake:2, Kiyoshi Teshigawara:2, Shuji Mori:3, Hideo K Takahashi:4, Nobuyuki Hirotsune:1, Shigeki Nishino:1, Masahiro Nishibori:2
1:Department of Neurological Surgery, Hiroshima City Hiroshima Citizens Hospital, Japan, 2:Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences., Japan, 3:Department of Pharmacology, School of Pharmacy, Shujitsu University, Japan, 4:Department of Pharmacology, Kinki University School of Medicine, Japan

BACKGROUND: High mobility group box-1 (HMGB1) plays an important role in triggering inflammatory responses in many types of diseases. Our previous study indicated that HMGB1 was present upstream of the secondary injury in traumatic brain injury (TBI). In addition, we described that anti-HMGB1 monoclonal antibody (mAb) efficiently and significantly reduced acute brain damage, such as BBB disruption, brain edema, and motor sensory dysfunction. This effect of anti-HMGB1 mAb persists for at least one week. In this study, we examine the sub-acute effect of anti-HMGB1 mAb on TBI.
METHODS: Traumatic brain injury was induced in rats by fluid percussion. Anti-HMGB1 mAb or control mAb was administered intravenously after TBI. Histochemical staining, plasma levels of HMGB1, impairment of motor activity and memory disturbance, and video electroencephalographic monitoring were evaluated 2 or 3 weeks after fluid percussion injury.
RESULTS: Anti-HMGB1 mAb remarkably inhibited the accumulation of the activated microglia/macrophage in the rat cortex in the ipsilateral hemisphere after TBI. Anti-HMGB1 mAb also prevented neuronal death in the rat hippocampus in the ipsilateral hemisphere after TBI. Treatment of rats with anti-HMGB1 mAb suppressed the impairment of motor functions, in association with the inhibition of HMGB1 translocation. The beneficial effects of anti-HMGB1 mAb on the motor and cognitive functions persisted for 14 days after injury. The effects of treatment with anti-HMGB1 mAb were also detected in electroencephalographic activity.
CONCLUSIONS: The beneficial effects of anti-HMGB1 mAb continued for sub-acute phase, suggesting that anti-HMGB1 mAb might prevent cognitive dysfunction after TBI.

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