Effect of recombinant ADAMTS-13 on microthrombosis and brain injury after experimental subarachnoid hemorrhage

Background 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. Objectives 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. Methods 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 20min after SAH; (iii) ADAMTS-13-/- mice (n=10); and (iv) ADAMTS-13-/- mice (n=10) treated with rADAMTS-13 20min after SAH. Mice were killed at 48h. Results are presented as means with standard errors of the mean. Results Infusion with rADAMTS-13 reduced the extent of microthrombosis by similar to 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). Conclusions Our results support the further study of rADAMTS-13 as a treatment option for the prevention of microthrombosis and brain injury after SAH.