title: Effect of recombinant ADAMTS-13 on microthrombosis and brain injury after experimental subarachnoid hemorrhage.
abstract: 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.
  
  
  OBJECTIVE
  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 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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Our results support the further study of rADAMTS-13 as a treatment option for the prevention of microthrombosis and brain injury after SAH.
authors.affiliation: 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.
authors.forename: M D I
authors.initials: MD
authors.lastname: Vergouwen
authors.forename: V L
authors.initials: VL
authors.lastname: Knaup
authors.forename: J J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.forename: O J
authors.initials: OJ
authors.lastname: de Boer
authors.forename: J C M
authors.initials: JC
authors.lastname: Meijers
mesh_terms: D051722:ADAM Proteins / Q000494:pharmacology*; D000071120:ADAMTS13 Protein; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D001930:Brain Injuries / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D002545:Brain Ischemia / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D019610:Cytoprotection; D004195:Disease Models, Animal; D006801:Humans; D020767:Intracranial Thrombosis / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D008666:Metalloendopeptidases / Q000172:deficiency / Q000235:genetics; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D013997:Time Factors
chemical_list: D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D051722:ADAM Proteins; C502939:ADAMTS13 protein, mouse; D008666:Metalloendopeptidases; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: ADAMTS13 protein, human; hemostasis; subarachnoid hemorrhage; thrombosis; von Willebrand factor