脑源性FGF20靶标脑血管对创伤性脑损伤的保护和修复作用及其机制研究

创伤性脑损伤（TBI）治疗的核心是保护继发性脑损伤的病理进展，明确以脑血管为靶标的继发性脑损伤病理机制，并寻找新的神经血管保护药物是TBI的一个重要研究方向。FGF20是一种脑源性的神经营养因子，有着独特的神经生物功能，尤其是对神经血管单元具有强大的保护和修复作用。我们前期动物实验发现，重组人FGF20可以明显减轻TBI小鼠血脑屏障的破坏，促进脑血管的再生和血管源性神经营养因子的分泌、修复神经元和少突胶质前体细胞的增殖。本项目拟从体内和体外水平上验证我们的理论假设：FGF20在TBI急性期能减轻血脑屏障的破坏，进而降低脑水肿、小胶质细胞激活和促炎因子的分泌，减少继发性神经元死亡；在亚急性期和修复期能促进脑血管再生、提高血管源性生长因子的分泌，从而促进内源性神经再生、白质重塑和长期神经功能的康复。本项目将深入阐明FGF20靶标脑血管治疗TBI的作用及机制，为TBI的治疗提供新的思路和方法。

The central purpose of traumatic brain injury (TBI) therapy is to protect against the pathological progress of secondary brain injury. To clarify the pathological mechanism of secondary brain injury centered on cerebrovascular target and to seek for new neurovascular protective compounds has become an important direction of TBI research. FGF20 is a kind of brain-derived neurotrophic factor with unique neurobiological function. Especially, it has powerful neurovascular unit protection and brain tissue repair effect. In our previous animal experiments, we found that recombinant human FGF20 could significantly reduce blood-brain barrier disruption, promote angiogenesis of cerebral vessels and vascular-derived neurotrophic factor secretion, repair and remodeling of white matter, and enhance long-term neurological function recovery of TBI in mice. By using in vivo TBI model and in vitro cell cultures, this project is aimed to test our hypothesis that in the acute phase of TBI, FGF20 can reduce blood-brain barrier damage, and consequently reduce brain edema, microglia/macrophage activation and pro-inflammatory factors secretion, and as well reduce the secondary neuronal death; in subacute/recovery phase of TBI, FGF20 may promote vascular-derived neurotrophic factor secretion, cerebrovascular angiogenesis, and neurogenesis, and improve white matter remodeling and long-term neurological function recovery. This project would help in understanding cerebrovascular targeting effects and underlying mechanisms, it would also provide new insight into cerebrovascular target strategy and new TBI therapy approach development.