ABSTRACT
Objective To study the dynamic expression and distribution of high mobility group box 1 (HMGB-1)in diffuse axonal injury (DAI)in rats and to clarify its involvement in the inflammatory reaction after DAI in rats,in order to provide new targets for the clinical treatment of DAI.Methods A DAI model was established using a coronal rotation device and evaluated by HE,Glees-Marsland silver staining,and Mallory phosphotungstic acid hematoxylin staining.Immunohistochemistry,Western blot and RT-PCR were used to detect the expression and distribution of HMGB-1 in the cortex of DAI rats at 6 h,1 d,3 d and 7 d.And TUNEL was used to examine the apoptosis of neurons in DAI rats.Results Immunohistochemical results showed that at 6 h and 1 d after DAI,the number of HMGB-1-positive cells decreased,but at 3 and 7 d it began to increase.Western blot also showed that during the early stage after DAI (6 h and 1 d),the level of HMGB-1 protein in the cortex was significantly lower than that in the control group,but at the late stage (3 and 7 d)after DAI it significantly increased compared with that in the control group until 7 d.RT-PCR showed that at 6 h after DAI there was no significant increase in the level of HMGB-1mRNA,but at 1 d there was a slight increase compared with the control group;at 3 and 7 d,it showed an obvious significance.TUNEL staining indicated that the significant neuronal apoptosis appeared as early as 6 h after DAI,and reached the peak at 3 d;it started to decrease at 7 d but still remained at a relatively high level.Conclusion The dynamic expression and distribution of HMGB-1 showed significant changes with the time course after DAI in rats.They decreased at the early stage but increased at the late stage.At the early stage, HMGB-1 is mainly passively released by the necrotic neurons,and at the late stage it may be actively secreted by the active inflammatory cells.HMGB-1 may mediate the post-DAI neural cell apoptosis by inducing the inflammatory reaction.