Early antagonism of cerebral high mobility group box-1 protein is benefit for sepsis induced brain injury
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Chao Ren1,2, Ya-Lin Tong3, Jun-Cong Li2, Ning Dong2, Ji-Wei Hao2, Qing-Hong Zhang2 and Yong-Ming Yao1,2,4
1School of Medicine, Nankai University, Tianjin 300071, People’s Republic of China
2Trauma Research Center, First Hospital Affiliated to The Chinese PLA General Hospital, Beijing 100048, People’s Republic of China
3Department of Burns and Plastic Surgery, The 181st Hospital of Chinese PLA, Guilin 541002, People’s Republic of China
4State Key Laboratory of Kidney Disease, The Chinese PLA General Hospital, Beijing 100853, People’s Republic of China
Yong-Ming Yao, email: [email protected]
Keywords: HMGB1, sepsis, lateral ventricles, antagonists, brain injuries
Received: July 29, 2016 Accepted: September 04, 2017 Published: October 05, 2017
Sepsis induced brain injury acts as an acute complication and accounts for deterioration and high mortality rate of septic condition. HMGB1 is a late inflammatory mediator that plays a critical role in brain dysfunction and diseases. However, the role of HMGB1 in sepsis induced brain dysfunction remains intricate. The current study investigated the effect of HMGB1 on brain injury in septic mice model with intracerebroventricular injection of BoxA (a specific antagonist of HMGB1). The expression of HMGB1, morphological changes of brain tissues, apoptosis of brain cells, and alteration of behavior were determined. The expressions of HMGB1 in cortex, hippocampus, and striatum were significantly enhanced in the sepsis group when compared with the sham group. In septic conditions, brain tissues showed significant abnormalities in tissue structure, and increased apoptosis of brain cells which was caspase-3 dependent. Septic mice showed suppression of locomotor activity and impairment of memory and learning. Neutralizing brain HMGB1 significantly improved brain injury and apoptosis of brain cells, and further ameliorated disturbed locomotor activities and damaged memory and learning. However, no significant improvement of survival rate was seen after inhibiting central HMGB1. These results reveal that HMGB1 is a potential target for ameliorating sepsis induced brain injury with early antagonizing.
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