1 Department of Neurosurgery, Houston Methodist Hospital, Houston, TX, USA.
2 Department of Systems Medicine & Bioengineering, Houston Methodist Research Institute, Houston, TX, USA.
J Cereb Blood Flow Metab. 2018 May;38(5):793-808. doi: 10.1177/0271678X17701157. Epub 2017 Mar 28.
Subarachnoid hemorrhage (SAH) in 95% of cases results in long-term disabilities due to brain damage, pathogenesis of which remains uncertain. Hindrance of cerebrospinal fluid (CSF) circulation along glymphatic pathways is a possible mechanism interrupting drainage of damaging substances from subarachnoid space and parenchyma. We explored changes in CSF circulation at different time following SAH and possible role of brain tissue factor (TF). Fluorescent solute and fluorescent microspheres injected into cisterna magna were used to track CSF flow in mice. SAH induced by perforation of circle of Willis interrupted CSF flow for up to 30 days. Block of CSF flow did not correlate with the size of hemorrhage. Following SAH, fibrin deposits were observed on the brain surface including areas without visible blood. Block of astroglia-associated TF by intracerebroventricular administration of specific antibodies increased size of hemorrhage, decreased fibrin deposition and facilitated spread of fluorophores in sham/naïve animals. We conclude that brain TF plays an important role in localization of hemorrhage and also regulates CSF flow under normal conditions. Targeting of the TF system will allow developing of new therapeutic approaches to the treatment of SAH and pathologies related to CSF flow such as hydrocephalus.
蛛网膜下腔出血（SAH）在 95%的情况下会导致脑损伤引起的长期残疾，其发病机制仍不清楚。脑脊液（CSF）沿神经胶质淋巴途径循环受阻是一种可能的机制，可中断蛛网膜下腔和实质中有害物质的引流。我们探讨了 SAH 后不同时间 CSF 循环的变化以及脑组织因子（TF）的可能作用。荧光溶质和荧光微球注入枕大池以追踪小鼠 CSF 的流动。Willis 环穿孔引起的 SAH 可中断 CSF 流动长达 30 天。CSF 流动的阻断与出血的大小无关。SAH 后，在包括无可见血液的区域在内的脑表面观察到纤维蛋白沉积。通过向侧脑室给予特异性抗体阻断星形胶质细胞相关 TF，增加了出血的大小，减少了纤维蛋白沉积，并促进了示踪剂在假手术/未处理动物中的扩散。我们得出结论，脑 TF 在出血的定位中起重要作用，并且在正常情况下还调节 CSF 流动。针对 TF 系统将允许开发新的治疗方法来治疗 SAH 和与 CSF 流动相关的病理学，如脑积水。
