基于复合损伤模型研究TRAP在脑外伤致神经功能障碍中的作用及机制

脑外伤（TBI）不仅造成神经功能障碍，还破坏骨骼代谢系统，增加病人骨折的风险。临床研究证实：相比单纯骨折，脑外伤伴骨折的复合损伤（MI）可以加速骨折愈合。但是，相比TBI，MI对神经功能的影响仍然存在争议。预实验发现，相比TBI，MI可以抑制脑组织炎症反应和神经元死亡。因此，本项目将运用多种生物学方法，以TRAP阳性的免疫细胞为切入点，拟解析：(1)TRAP在MI中脑损伤病理过程中的角色；(2)TRAP调控MI中脑组织程序性细胞死亡的机制；(3)TRAP对TBI致神经功能障碍的影响及机制。最终阐明通过精准激活TRAP，激发免疫细胞更强的吞噬功能，避免过度炎症（神经炎症）和神经细胞死亡，促进神经功能的恢复。以上研究成果拟证实MI中脑损伤更轻微的结果及潜在机制，提出精准激活免疫细胞治疗TBI的新理念和有效靶点（TRAP）。

Traumatic brain injury (TBI) leads to the dysfunction of central nervous system, as well as the destruction of skeletal metabolic system, thus increasing the risk of bone fracture. Previous clinical studies have found that TBI with fracture (MI) could accelerate fracture healing compared with isolated fracture. However, comparing with isolated TBI, the effect of MI on neurological function is still remained controversial. Our pilot study found that MI inhibited the neuroinflammation and neuronal death in the acute phage compared with TBI only. Therefore, this project will use a variety of biological methods, and focus on the tartrate resistant acid phosphatase (TRAP) positive immune cells to explore and analyze: (1) the role of TRAP in the pathological process of brain injury in the MI model; (2) the regulatory mechanism of TRAP on programmed cell death in the brain tissues of the MI model; (3) the mechanisms of TRAP in regulating neurological deficits post-TBI. This project will finally clarify that the phagocytosis mediated by TRAP activated precisely is enhanced to avoid excessive inflammation (neuroinflammation) and brain damage (pyroptosis), and consequently the promoted recovery of neurological functions. These results will confirm the fact that brain injury is slighter in the MI model and its potential mechanisms, and provide a new concept which is activating immune cells precisely and a novel target (TRAP) for clinical TBI treatment.