| Background and Objective Some patients with post-traumatic brain injury(TBI)have cognitive impairment,including mild cognitive impairment(MCI)and dementia.The prognosis of patients with severe TBI is poor,and most of them are in coma,so it is difficult to monitor their cognitive ability.With the progress of medicine,the prognosis of patients with mild and moderate TBI has been improved significantly,and people begin to pay attention to the quality of life.However,the complication of MCI in these patients in the late stage after TBI is always hidden in clinic.If MCI progresses to dementia stage,it will seriously affect the quality of life of patients.At present,there is no unified standard for standardized clinical treatment of MCI combined after TBI,and there is deficiency of basic research.Previous studies have shown that HMGB1/TLR pathway and HMGB1/RAGE pathway are closely related to non-infectious inflammation in the brain,and their abnormal expression is associated with cognitive impairment.The purpose of this study was to explore the significance of HMGB1/TLR2 in combined MCI after mild and moderate TBI,providing theoretical basis for the development of MCI and improving the prognosis of patients.Methods From January 2016 to February 2018,122 patients with mild and moderate TBI that is Glasgow Coma Scale(GCS)of 9-15 were prospectively enrolled in the Neurosurgery of Hospital of the Fifth Affiliated Hospital of Zhengzhou University,and 40 healthy adults who met the criteria for outpatient physical examination were selected as healthy group.The serum levels of HMGB1,TLR2,TLR4 and RAGE were measured by double antibody sandwich enzyme-linked immunosorbent assay(ELISA)in healthy group and TBI group,meanwhile the expression of HMGB1,TLR2 and RAGE in each subgroup was analyzed.Results 1.After 1,2 and 3 months,the serum levels of HMGB1,TLR2,TLR4 and RAGE in mild and moderate TBI group were significantly higher than those in healthy group(all P < 0.05);after 1 and 2 months,the serum levels of HMGB1 and TLR4 in mild TBI group were significantly higher than those in mild TBI group(all P< 0.05),but there was no significant difference in the levels of TLR2 and RAGE(all P > 0.05);after 3 months,the serum levels of HMGB1 and TLR4 in mild TBI group were significantly higher than those in mild TBI The levels of TLR2,TLR4 and RAGE in TBI group were not significantly different from those in serum(P> 0.05).The serum levels of HMGB1 and TLR2 were higher in mild TBI with MCI group and moderate TBI with MCI group than those in mild TBI without MCI group and moderate TBI without MCI group after 1 and 2 months(all P< 0.05),and there was no significant difference in RAGE level(all P> 0.05).Two months later,the serum levels of TLR4 in moderate TBI without MCI group were higher than those in mild TBI with MCI group(P> 0.05).The levels of HMGB1 and TLR2 in serum of MCI group and MCI group were higher than those of TLR4 group(P< 0.05).There was no significant difference between MCI group and MCI group(P> 0.05).Three months later,the levels of HMGB1 and TLR2 in serum of MCI group and MCI group were higher than those of MCI group and MCI group without MCI group.There was no significant difference in the levels of TLR4 and RAGE(P> 0.05).There was no significant difference in the levels of HMGB1 and TLR2 between mild TBI with MCI group and moderate TBI with MCI group after 1,2 and 3 months(P > 0.05).2.After 1,2 and 3 months,the serum levels of TLR2 and HMGB1 were positively correlated in patients with craniocerebral injury and MCI,Y=0.414X-1.236(r=0.725,P=0.000),Y=0.414X-0.855(r=0.773,P=0.000),Y=0.365X-0.384(r=0.813,P=0.000);but TLR4 and RAGE were not significantly correlated with HMGB1(r=0.345,0.267,0.362,0.331,0.297,0.322,均 P > 0.05).3.We performed ROC Curve to evaluate predictive value of HMGB1,TLR2,TLR2,TLR4,TLR4 and RAGE in TBI patients with secondary MCI was analyzed by ROC curve analysis.After 1 month,HMGB1: AUC = 0.784(95% CI 0.642-0.891,95% CI 0.642-0.891,P=0.000);TLR2: AUC = 0.675(95% CI 0.583-0.583-0.769,P=0.000);TLR4: AUC = 0.522(95% CI 0.522(95% CI 0.414-0.414-0.625,TLR4,TLR4 and RAGE=0.625 496(95% CI 0.428-0.576,P=0.452).After 2 months,HMGB1: AUC=0.821(95% CI 0.785-0.855,P=0.000);TLR2: AUC=0.721(95% CI 0.605-0.834,P=0.000);TLR4: AUC=0.535(95% CI 0.452-0.676,P=0.136);RAGE: AUC=0.514(95% CI 0.452-0.579,P=0.498).After 3 months,HMGB1: AUC=0.717(95%CI 0.653-0.772,P=0.000);TLR2: AUC=0.762(95%CI 0.706-0.819,P=0.000);TLR4: AUC=0.484(95%CI 0.406-0.573,P=0.000);RAGE: AUC=0.509(95% CI 0.462-0.561,P=0.000).Conclusions 1.The activation of HMGB1-TLR2/TLR4/RAGE pathway after traumatic brain injury results in high expression of HMGB1,TLR2,TLR4 and RAGE in the serum of patients.The activation of HMGB1-TLR4 pathway is more significant with the severity of TBI.2.The high expression of HMGB1 and TLR2 in MCI secondary to traumatic brain injury and their positive correlationship suggest that HMGB1-TLR2 pathway may play an important role in this pathological process. |
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