急性重症脑静脉窦血栓静脉性脑梗死的机制及干预研究

Venous cerebral infarction plays a key role in the development of acute severe intracranial cerebral venous sinus thrombosis (CVST). There existing a big difference between cerebral venous infarction (CVI) and arterial infarction. CVI generally develops much slower than arterial stroke. Further, areas with moderate reduction of cortical blood flow causing a penumbra-like area surrounding a core infarct in CVI are wider than in arterial stroke. Therefore, therapeutic window in time and space is delayed and is much wider in CVI. One important feature of CVI in CVST is over expression of vascular endothelial growth factor (VEGF), which is thought to be the reason of dural arteriovenous fistulas (DAVF).But VEGF also increases vascular permeability, which could cause brain edema and cell damage. But VEGF expression is mediated by Hypoxia inducible factor (HIF-1) and HIF-1 can also upregulate MMP activity which is closely related to blood brain barrier (BBB) disruption and cerebral hemorrhage. In this study, we try to build an animal model of acute severe CVST, and investigate the molecular mechanism of CVI. Aiming at the key role of CVI, besides mechanical thrombolysis, we incorporated into therapeutic hypothermia measures for the treatment of acute severe CVST.

静脉性脑梗死是急性重症颅内静脉窦血栓形成（CVST）病情演变的一个重要环节，它与动脉性脑梗死有很大的区别，表现为脑缺血的时间窗较宽，缺血半暗带范围大。CVST静脉性脑梗死的很重要特点就是血管内皮生长因子（VEGF）的大量表达，它被认为是导致CVST演变为硬脑膜动静脉瘘的重要原因，但是VEGF也是重要的血管通透性调节因子，它能促使血管通透性增加，加重脑水肿和细胞损伤。而低氧诱导因子（HIF-1）是VEGF表达的上游调节因子，除此之外，HIF-1还能上调基质金属蛋白酶（MMP）的活性及促进细胞凋亡等作用，MMP活性升高则与血脑屏障破坏、脑出血密切相关。本研究通过建立急性重症CVST的动物模型，探索静脉性脑梗死的分子生物学机制，阐明它们在时间、空间上的演变规律。针对静脉性脑梗死关键环节，在强化静脉窦血栓机械碎栓基础上，引入亚低温的干预措施，为急性重症CVST的临床干预，提供新的治疗思路。

静脉性脑梗死是急性重症颅内静脉窦血栓形成（CVST）病情演变的一个重要环节，它与动脉性脑梗死有很大的区别，表现为脑缺血的时间窗较宽，缺血半暗带范围大。CVST 静脉性脑梗死的很重要特内皮生长因子（VEGF）的大量表达，它被认为是导致CVST 演变为硬脑膜动静脉瘘的重要原因，但是VEGF 也是重要的血管通透性调节因子，它能促使血管通透性增加，加重脑水肿和细胞损伤。而低氧诱导因子（HIF-1）是VEGF 表达的上游调节因子，除此之外，HIF-1 还能上调基质金属蛋白酶（MMP）活性及促进细胞凋亡等作用，MMP 活性升高则与血脑屏障破坏、脑出血密切相关。本课题建立了急性重症CVST 的动物模型，探索静脉性脑梗死的分子生物学机制，阐明它们在时间、空间上的演变规律。针对静脉性脑梗死关键环节，在强化静脉窦血栓机械碎栓基础上，引入亚低温的干预措施，得到了初步的结果，为急性重症CVST 的临床干预，提供新的治疗思路。