脊髓损伤是骨科临床尚未解决的难题之一。新近研究表明,巨噬细胞活化诱导的血管新生对周围神经损伤修复具有关键作用。受此启发，本研究拟探讨巨噬细胞活化在促进脊髓损伤后血管新生中的作用及可能机制。课题组前期通过体外实验观察到巨噬细胞来源的VEGFA对血管新生具有调控作用，本研究拟进一步探讨其调控是否通过激活HIF-1α-VEGFA 通路来实现。并建立C57BL/6小鼠改良Allen’s脊髓损伤模型，应用腺病毒转染VEGFA促脊髓损伤后血管新生，通过免疫组化、激光散斑血流成像及Micro-CT等检测新生血管形成；通过行为学、电生理、组织学及fMRI检测神经功能恢复情况，从多角度来综合评价促血管新生在脊髓损伤修复中的作用。最后通过建立巨噬细胞VEGFA敲入/敲除小鼠模型，明确脊髓损伤后巨噬细胞诱导的血管新生是否对神经再生具有始动作用及其可能机制，进而可望为临床脊髓损伤患者的修复重建奠定实验基础。

Spinal cord injury is still a great challenge for orthopedic surgeons. Recent studies have revealed that macrophage-induced angiogenesis is vital for peripheral nerve repair after injury. The main purpose of this study is to explore the role and mechanism of macrophage activation in promoting angiogenesis after acute spinal cord injury. In our previous research, the regulation of macrophage-induced VEGFA for angiogenesis was investigated in vitro. According to the in-vitro results, this study intends to further explore whether its regulation is achieving by activating HIF-1α-VEGFA pathway. Then, the modified Allen's model of spinal cord injury on C57BL/6 mice was established. Adenoviruses, expressing VEGFA, were transfected after spinal cord injury to promote angiogenesis. The angiogenic efficacy will be assessed comprehensively by immunohistochemistry, laser speckle flow imaging and Micro-CT angiography. The viability and function of neurons in spinal cord will be further determined by behavioral testing, electrophysiology testing, and fMRI. Finally, the relationship between macrophage, angiogenesis and neuron regeneration after spinal cord injury will be further proved by conditional knock-in/ knock-out mouse models. This study is expected to be able to elucidate the mechanistic role of macrophage-induced angiogenesis in neural repair and provide fundamental knowledge for translation into clinical practice and developing future therapies for patients.