Role of inhibition of phosphorylated Cx43 by PKA pathway in treatment for traumatic brain injury

CHEN Wei; ZHENG Ping; REN Da-Bin; TONG Wu-Song; LIU Ning; ZHAO Lin

Abstract：Objective To investigate the effect of inhibition of phosphorylated connexin (Cx)43 by protein kinase A (PKA) on the treatment of traumatic brain injury (TBI).Methods One hundred and twenty rats were randomly divided into 6 groups of 20 animal each,i.e.sham operation group,treatment groups,1,2 and 3 in which the rats received peritoneal injection of 20,40 and 60 mg/kg 8-Bromo-cAMP respectively 1 hour after TBI,vehicle group in which the rats received peritoneal injection of dimethyl sulphoxide 1 hour after TBI and TBI group in which the rats underwent TBI only and did not receive any treatment.TBI models were established with fluid percussion device in the rats.Ten rates were sacrificed 48 hours after TBI and their brain water content was determined after the behavioral disordes were determined by Neurological Severity score (NSS) in all the groups.Another 10 rates were sacrificed 48 hours after TBI and their hippocampal astorcytes were obtained in order to determine the expressions of extracellular regulated protein kinase (ERK)1/2,nonphorylated (NP)-Cx43,glutamic transducin (GLT)-1 and Na-K-ATP determined by western blot and glutamic acid (Glu) by high pressure liquid chromatography.Result The levels of NP-Cx43,GLT-1 and Na-K-ATP expressions were significantly higher in all the treatment groups and sham operation group than those in other two groups (P＜0.05).The levels of ERK1/2 and Glu expressions,brain water content and the scores of NSS were significantly lower in all the treatment groups and sham operation operation group than those in the TBI and vehicle groups (P＜0.05).These changes were 8-Bromo-cAMP dose-dependent.Conclusions Activation of PKA pathway can inhibit ERK1/2 pathway,and up-regulate the levels of NP-Cx43,GLT-1 and Na-K-ATP protein expressions in the hippocampal astrocytes,which can reduce the contents of brain water and Glu on the brain in the rate with TBI.