Protective effects of dexmedetomidine from brain injury in septic mice

Objective To investigate the effect of dexmedetomidine on brain injury in septic mice. Methods One hundred and eighty 6- 8-week-old ICR( institute of cancer research) mice,weighing 20- 25 g,were randomly divided into 4 groups: sham( S)group,sham + dexmedetomidine group( S + D),cecal ligation and puncture( CLP) group and cecal ligation and puncture + dexmedetomidine( CLP + D) group. Sepsis was produced by cecal ligation and puncture( CLP). The mice were intraperitoneally injected with dexmedetomidine 20 μg / kg at 0,3 and 6 h after CLP or sham operation,respectively. At 6,12 and 24 h after CLP or sham operation,brain tissues were removed to detect the exudation of evans blue( EB) and water contents,and the concentration of TNF-α and HMGB1. At 24 h after CLP or sham operation,the expression of ZO-1 and Claudin-5 in brain tissues was detected by Western blot and the histopathologic changes were observed by hematoxylin-eosin staining. Results There was no statistical difference in all aspects between S group and S + D group( P 0. 05). Compared with S group,the contents of EB and water and the concentrations of TNF-α and HMGB1 in brain tissues were significantly increased in CLP group at 6,12 and 24 h after CLP operation( P 0. 05),while the expression of ZO-1and Claudin-5 in brain tissues was significantly decreased at 24 h after CLP operation( P 0. 05). The loosen arrangement,dark cytoplasm and nuclear pyknosis were observed in the hippocampal CA1 region in CLP group at 24 h after CLP operation. Compared with CLP group,the contents of EB and water and the concentrations of TNF-α and HMGB1 in brain tissues were significantly decreased in CLP + D group at 6,12 and 24 h after CLP operation( P 0. 05),while the expression of ZO-1 and Claudin-5 in brain tissues was significantly increased at 24 h after CLP operation( P 0. 05). The arrangement of neurons was nearly regular and the damaged neurons were decreased in the hippocampal CA1 region in CLP + D group at 24 h after CLP operation. Conclusion Dexmedetomidine can alleviate brain injury via lightening the blood-brain barrier disruption in septic mice,which may be related to the inhibition of inflammation response.