脑室出血（IVH）是自发性脑出血中最严重的类型，现有治疗措施均难以显著改善IVH患者的神经功能预后。因此，深入研究IVH继发性脑损伤、探索有效的治疗方式具有重要的临床意义。本研究组通过预实验发现大鼠IVH后出现纤维蛋白可在血管周围间隙堆积，并伴随脑脊液无法经“血管周围间隙-Glymphatic系统”再循环进入脑组织的现象，同时IVH后脑组织β-Amyloid等大分子物质大量表达。本课题拟在此基础上，通过脑脊液示踪、溶质大分子示踪的方法，证明IVH后纤维蛋白堵塞血管周围间隙可导致脑脊液经Glymphatic系统对β-Amyloid等溶质大分子的清除功能障碍。再基于Glymphatic系统阻塞，分析β-Amyloid异常堆积与IVH继发性脑损伤的关系；最后进一步以tPA溶解血管周围间隙内纤维蛋白、改善Glymphatic系统的清除功能作为干预方式，探索tPA对IVH继发性脑损伤的治疗作用。

Intraventricular hemorrhage (IVH) is proven to be the independent negative prognostic factor for patients with spontaneous intracerebral hemorrhage. The mechanism of secondary brain injury in IVH remains unclear, which causes the current managements being ineffective in improving the neurological functional outcome of these patients. Therefore, further investigation on secondary brain injury of IVH and exploration of effective treatment are of great importance. According to our preliminary study on IVH rat model, amount of fibrinogen was observed accumulating in whole-brain subarachnoid space and paravascular space, and the patency of paravascular pathway of cerebrospinal fluid recirculation was blocked. In the meantime, a significant aggregation of β-Amyloid, a large molecular toxic material, was observed in IVH model. In the next step, we are going to testify the hypothesis that blockage of cerebrospinal fluid recirculation caused by accumulation of blood clot in paravascular space may responsible for the Glymphatic dysfunction. And after Glymphatic dysfunction, β-Amyloid aggregation may occur and contribute to the severe secondary brain injury in IVH. Moreover, we are trying to investigate the potential role of tissue-type plasminogen activator (tPA) in relieving severe secondary brain injury in IVH via fibrinolysis of blood clot in paravascular space and improving the function of Glymphatic system.