Abstract：
BACKGROUND: Traumatic brain injury (TBI), as a major public health problem, is characterized by high incidence rate, disability rate, and mortality rate. Neuroinflammation plays a crucial role in the pathogenesis of TBI. Triggering receptor expressed on myeloid cells-1 (TREM-1) is recognized as an amplifier of the inflammation in diseases of the central nervous system (CNS). However, the function of TREM-1 remains unclear post-TBI. This study aimed to investigate the function of TREM-1 in neuroinflammation induced by TBI.
METHODS: Brain water content (BWC), modified neurological severity score (mNSS), and Morris Water Maze (MWM) were measured to evaluate the effect of TREM-1 inhibition on nervous system function and outcome after TBI. TREM-1 expression in vivo was evaluated by Western blotting. The cellular localization of TREM-1 in the damaged region was observed via immunofluorescence staining. We also conducted Western blotting to examine expression of SYK, p-SYK and other downstream proteins.
RESULTS: We found that inhibition of TREM-1 reduced brain edema, decreased mNSS and improved neurobehavioral outcomes after TBI. It was further determined that TREM-1 was expressed on microglia and modulated subtype transition of microglia. Inhibition of TREM-1 alleviated neuroinflammation, which was associated with SYK/p38MAPK signaling pathway.
CONCLUSIONS: These findings suggest that TREM-1 can be a potential clinical therapeutic target for alleviating neuroinflammation after TBI.
METHODS: Brain water content (BWC), modified neurological severity score (mNSS), and Morris Water Maze (MWM) were measured to evaluate the effect of TREM-1 inhibition on nervous system function and outcome after TBI. TREM-1 expression in vivo was evaluated by Western blotting. The cellular localization of TREM-1 in the damaged region was observed via immunofluorescence staining. We also conducted Western blotting to examine expression of SYK, p-SYK and other downstream proteins.
RESULTS: We found that inhibition of TREM-1 reduced brain edema, decreased mNSS and improved neurobehavioral outcomes after TBI. It was further determined that TREM-1 was expressed on microglia and modulated subtype transition of microglia. Inhibition of TREM-1 alleviated neuroinflammation, which was associated with SYK/p38MAPK signaling pathway.
CONCLUSIONS: These findings suggest that TREM-1 can be a potential clinical therapeutic target for alleviating neuroinflammation after TBI.
摘要：
背景：创伤性脑损伤（TBI），作为一个重大的公共卫生问题，其特点是发病率高，残疾率,和死亡率。神经炎症在TBI的发病机制中起着至关重要的作用。在骨髓细胞上表达的触发受体-1（TREM-1）被认为是中枢神经系统（CNS）疾病中炎症的放大器。然而,TREM-1的功能在TBI后仍不清楚。本研究旨在探讨TREM-1在TBI诱导的神经炎症中的作用。
方法：脑含水量（BWC），改良神经严重度评分（mNSS），测量和Morris水迷宫（MWM）以评估TREM-1抑制对TBI后神经系统功能和结果的影响。通过Western印迹评估体内TREM-1表达。通过免疫荧光染色观察TREM-1在受损区域的细胞定位。我们还进行了蛋白质印迹检测SYK的表达，p-SYK和其他下游蛋白。
结果：我们发现抑制TREM-1可以减少脑水肿，TBI后mNSS降低，神经行为结局改善。进一步确定TREM-1在小胶质细胞上表达并调节小胶质细胞的亚型转变。抑制TREM-1减轻神经炎症，与SYK/p38MAPK信号通路有关。
结论：这些发现提示TREM-1可能是缓解TBI后神经炎症的潜在临床治疗靶点。
方法：脑含水量（BWC），改良神经严重度评分（mNSS），测量和Morris水迷宫（MWM）以评估TREM-1抑制对TBI后神经系统功能和结果的影响。通过Western印迹评估体内TREM-1表达。通过免疫荧光染色观察TREM-1在受损区域的细胞定位。我们还进行了蛋白质印迹检测SYK的表达，p-SYK和其他下游蛋白。
结果：我们发现抑制TREM-1可以减少脑水肿，TBI后mNSS降低，神经行为结局改善。进一步确定TREM-1在小胶质细胞上表达并调节小胶质细胞的亚型转变。抑制TREM-1减轻神经炎症，与SYK/p38MAPK信号通路有关。
结论：这些发现提示TREM-1可能是缓解TBI后神经炎症的潜在临床治疗靶点。
