Department of Neurology and Neurosurgery, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
J Thromb Haemost. 2014 Jun;12(6):943-7. doi: 10.1111/jth.12574.
A common complication after aneurysmal subarachnoid hemorrhage (SAH) is delayed cerebral ischemia (DCI), which is associated with vasospasm and other mechanisms such as microthrombosis. ADAMTS-13 activity plays a role in the prevention of thrombus formation in the cerebral microvasculature. Previously, we observed that patients with DCI have lower levels of ADAMTS-13.
To examine whether recombinant human ADAMTS-13 (rADAMTS-13) reduces cerebral microthrombus formation and brain injury in an experimental mouse model of SAH including wild-type and ADAMTS-13(-/-) mice.
Experimental SAH was induced with the prechiasmatic blood injection model. The following experimental groups were investigated: (i) C57BL/6J mice (n = 10); (ii) C57BL/6J mice (n = 10) treated with rADAMTS-13 20 min after SAH; (iii) ADAMTS-13(-/-) mice (n = 10); and (iv) ADAMTS-13(-/-) mice (n = 10) treated with rADAMTS-13 20 min after SAH. Mice were killed at 48 h. Results are presented as means with standard errors of the mean.
Infusion with rADAMTS-13 reduced the extent of microthrombosis by ~ 50% in both wild-type mice (mean fibrinogen area: 0.28% ± 0.09% vs. 0.15% ± 0.04%; P = 0.20) and ADAMTS-13(-/-) mice (mean fibrinogen area: 0.32% ± 0.05% vs. 0.16% ± 0.03%; P = 0.016). In addition, rADAMTS-13 reduced brain injury by > 60% in both wild-type mice (mean microglia area: 0.65% ± 0.18% vs. 0.18% ± 0.04%; P = 0.013) and ADAMTS-13(-/-) mice (mean microglia area: 1.24% ± 0.36% vs. 0.42% ± 0.13%; P = 0.077).
Our results support the further study of rADAMTS-13 as a treatment option for the prevention of microthrombosis and brain injury after SAH.
动脉瘤性蛛网膜下腔出血（SAH）后常见的并发症是迟发性脑缺血（DCI），其与血管痉挛和微血栓形成等机制有关。ADAMTS-13 活性在预防脑微血管内血栓形成中发挥作用。先前，我们观察到 DCI 患者的 ADAMTS-13 水平较低。
检查重组人 ADAMTS-13（rADAMTS-13）是否可减少实验性 SAH 小鼠模型中的脑微血栓形成和脑损伤，该模型包括野生型和 ADAMTS-13（-/-）小鼠。
通过前视交叉血管内注射模型诱导实验性 SAH。研究了以下实验组：（i）C57BL/6J 小鼠（n = 10）；（ii）SAH 后 20 分钟给予 rADAMTS-13 的 C57BL/6J 小鼠（n = 10）；（iii）ADAMTS-13（-/-）小鼠（n = 10）；和（iv）SAH 后 20 分钟给予 rADAMTS-13 的 ADAMTS-13（-/-）小鼠（n = 10）。在 48 小时处死小鼠。结果表示为均数±标准误。
在野生型小鼠中，rADAMTS-13 输注将微血栓形成的程度降低了约 50%（纤维蛋白原面积：0.28%±0.09% vs. 0.15%±0.04%；P = 0.20）和 ADAMTS-13（-/-）小鼠（纤维蛋白原面积：0.32%±0.05% vs. 0.16%±0.03%；P = 0.016）。此外，rADAMTS-13 将野生型小鼠的脑损伤降低了超过 60%（小胶质细胞面积：0.65%±0.18% vs. 0.18%±0.04%；P = 0.013）和 ADAMTS-13（-/-）小鼠（小胶质细胞面积：1.24%±0.36% vs. 0.42%±0.13%；P = 0.077）。
我们的结果支持进一步研究 rADAMTS-13 作为预防 SAH 后微血栓形成和脑损伤的治疗选择。
