硬脑膜淋巴管物质引流和免疫调控功能在脑创伤中的作用及相关机制研究

硬脑膜淋巴管（mLVs）与脑病关系倍受瞩目，但少见其在脑创伤(TBI)中的功能作用研究。已知mLVs引流障碍会加重TBI，却有证据表明抑制mLVs引流可减少颈淋巴结淋巴细胞的脑源炎性特征、减轻神经损伤。申请人证实TBI早期抑制淋巴细胞迁移可减轻神经损伤且掌握了mLVs示踪和引流调控技术。故假说：TBI后增强mLVs引流具有清除脑损伤毒性物质和促进颈淋巴结内淋巴细胞获得脑源性抗原递呈的双重作用，早期加强mLVs引流联合抑制淋巴细胞迁移可促进神经功能修复。拟依托TBI小鼠模型，以神经功能检测、调控mLVs引流、抑制淋巴细胞迁移和转录组测序等技术，探明①TBI后调节mLVs引流和颈部淋巴结淋巴细胞迁移活化功能的神经保护作用；②TBI后颈淋巴结T淋巴细胞获得脑源性抗原递呈在TBI后损伤修复的关键作用；③T淋巴细胞的关键转录组信息及其与TBI神经损伤和修复关系。为创新TBI诊疗策略奠定基础。

The relationship between meningeal lymphatic vessels (mLVs) and encephalopathy has attracted much attention, but its functional role in traumatic brain injury (TBI) is rarely studied. It is known that mLVs drainage disorder will aggravate TBI, but there is evidence that inhibiting mLVs drainage can decrease the encephalitogenic property of the lymphocytes in the cervical lymph nodes and improve the neural injury. The applicant confirmed that the inhibition of lymphocytes migration in the early stage of TBI could alleviate nerve injury and mastered the techniques of mLVs tracing and drainage regulation. Therefore, the hypothesis is that the enhancement of mLVs drainage after TBI has the dual effects on both removing toxic substances of injured brain tissue and promoting the brain-derived antigen presentation to the lymphocytes in cervical lymph nodes. The early strengthening mLVs drainage combined with the lymphocytes migration inhibition after TBI, could prompting the repair of the neural damage. Relying on TBI mouse model and performing the neural function tests, regulation of mLVs drainage, inhibition of lymphocyte migration and transcriptome sequencing, we will detect 1. the neuroprotective effects on TBI of the regulation either single or both of mLVs drainage and the lymphocytes migration and activation in the cervical lymph nodes. 2. The key role in neural injury recovery of T lymphocytes in the cervical lymph nodes after TBI, which are presented with the brain-derived antigens. 3. The key transcriptome information of these T lymphocytes and its relationship with the neural injury and repair after TBI. The research will lay the foundation for the innovation of TBI diagnosis and treatment strategy.