scholarly journals Beneficial Effects of Ethyl Pyruvate through Inhibiting High-Mobility Group Box 1 Expression and TLR4/NF-κB Pathway after Traumatic Brain Injury in the Rat

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Xingfen Su ◽  
Handong Wang ◽  
Jinbing Zhao ◽  
Hao Pan ◽  
Lei Mao
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Ethyl Pyruvate ◽  
Apoptotic Cell ◽  
High Mobility ◽  
High Mobility Group ◽  
Male Rats ◽  
Vehicle Group ◽  
Secondary Brain Injury ◽  
Protective Effects

Ethyl pyruvate (EP) has demonstrated neuroprotective effects against acute brain injury through its anti-inflammatory action. The nuclear protein high-mobility group box 1 (HMGB1) can activate inflammatory pathways when released from dying cells. This study was designed to investigate the protective effects of EP against secondary brain injury in rats after Traumatic Brain Injury (TBI). Adult male rats were randomly divided into three groups: (1) Sham + vehicle group, (2) TBI + vehicle group, and (3) TBI + EP group (n=30per group). Right parietal cortical contusion was made by using a weight-dropping TBI method. In TBI + EP group, EP was administered intraperitoneally at a dosage of 75 mg/kg at 5 min, 1 and 6 h after TBI. Brain samples were harvested at 24 h after TBI. We found that EP treatment markedly inhibited the expressions of HMGB1 and TLR4, NF-κB DNA binding activity and inflammatory mediators, such as IL-1β, TNF-αand IL-6. Also, EP treatment significantly ameliorated beam walking performance, brain edema, and cortical apoptotic cell death. These results suggest that the protective effects of EP may be mediated by the reduction of HMGB1/TLR4/NF-κB-mediated inflammatory response in the injured rat brain.

scholarly journals HMGB1 a-Box Reverses Brain Edema and Deterioration of Neurological Function in a Traumatic Brain Injury Mouse Model

2018 ◽  
Vol 46 (6) ◽  
pp. 2532-2542 ◽  
Author(s):  
Lijun Yang ◽  
Feng Wang ◽  
Liang Yang ◽  
Yunchao Yuan ◽  
Yan Chen ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Brain Edema ◽  
Therapeutic Potential ◽  
High Mobility ◽  
Neurological Injury ◽  
Secondary Brain Injury ◽  
Cell Degeneration ◽  
Injured Brain ◽  
Walking Tests

Background/Aims: Traumatic brain injury (TBI) is a complex neurological injury in young adults lacking effective treatment. Emerging evidences suggest that inflammation contributes to the secondary brain injury following TBI, including breakdown of the blood brain barrier (BBB), subsequent edema and neurological deterioration. High mobility group box-1 (HMGB1) has been identified as a key cytokine in the inflammation reaction following TBI. Here, we investigated the therapeutic efficacy of HMGB1 A-box fragment, an antagonist competing with full-length HMGB1 for receptor binding, against TBI. Methods: TBI was induced by controlled cortical impact (CCI) in adult male mice. HMGB1 A-box fragment was given intravenously at 2 mg/kg/day for 3 days after CCI. HMGB1 A-box-treated CCI mice were compared with saline-treated CCI mice and sham mice in terms of BBB disruption evaluated by Evan’s blue extravasation, brain edema by brain water content, cell death by propidium iodide staining, inflammation by Western blot and ELISA assay for cytokine productions, as well as neurological functions by the modified Neurological Severity Score, wire grip and beam walking tests. Results: HMGB1 A-box reversed brain damages in the mice following TBI. It significantly reduced brain edema by protecting integrity of the BBB, ameliorated cell degeneration, and decreased expression of pro-inflammatory cytokines released in injured brain after TBI. These cellular and molecular effects were accompanied by improved behavioral performance in TBI mice. Notably, HMGB1 A-box blocked IL-1β-induced HMGB1 release, and preferentially attenuated TLR4, Myd88 and P65 in astrocyte cultures. Conclusion: Our data suggest that HMGB1 is involved in CCI-induced TBI, which can be inhibited by HMGB1 A-box fragment. Therefore, HMGB1 A-box fragment may have therapeutic potential for the secondary brain damages in TBI.

scholarly journals Anti-high Mobility Group Box-1 Antibody Therapy for Traumatic Brain Injury

2014 ◽  
Vol 134 (6) ◽  
pp. 701-705 ◽  
Author(s):  
Yu Okuma ◽  
Isao Date ◽  
Masahiro Nishibori
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Antibody Therapy ◽  
High Mobility ◽  
High Mobility Group

scholarly journals High Mobility Group Box 1 and Traumatic Brain Injury

2017 ◽  
Vol 07 (02) ◽  
pp. 50-61 ◽  
Author(s):  
Seidu A. Richard ◽  
Wu Min ◽  
Zhaoliang Su ◽  
Huaxi Xu
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
High Mobility ◽  
High Mobility Group

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

2018 ◽  
Vol 527 (6) ◽  
pp. 1102-1117 ◽  
Author(s):  
Kyria M. Webster ◽  
Mujun Sun ◽  
Peter J. Crack ◽  
Terence J. O'Brien ◽  
Sandy R. Shultz ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
High Mobility ◽  
High Mobility Group ◽  
Age Dependent

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

2019 ◽  
Vol 122 ◽  
pp. e864-e871 ◽  
Author(s):  
Yu Okuma ◽  
Hidenori Wake ◽  
Kiyoshi Teshigawara ◽  
Yu Takahashi ◽  
Tomohito Hishikawa ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Cognitive Dysfunction ◽  
Antibody Therapy ◽  
High Mobility ◽  
High Mobility Group

scholarly journals Minocycline Attenuates High Mobility Group Box 1 Translocation, Microglial Activation, and Thalamic Neurodegeneration after Traumatic Brain Injury in Post-Natal Day 17 Rats

2018 ◽  
Vol 35 (1) ◽  
pp. 130-138 ◽  
Author(s):  
Dennis W. Simon ◽  
Rajesh K. Aneja ◽  
Henry Alexander ◽  
Michael J. Bell ◽  
Hülya Bayır ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Microglial Activation ◽  
High Mobility ◽  
High Mobility Group
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