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

Summary 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 microva...

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Bibliographic Details
Published in:Journal of thrombosis and haemostasis Vol. 12; no. 6; pp. 943 - 947
Main Authors: Vergouwen, M. D. I., Knaup, V. L., Roelofs, J. J. T. H., Boer, O. J., Meijers, J. C. M.
Format: Journal Article
Language:English
Published: England Elsevier Limited 01.06.2014
Subjects:
ADAM Proteins - pharmacology
ADAMTS13 Protein
ADAMTS13 protein, human
Animals
Brain - drug effects
Brain - pathology
Brain Injuries - diagnosis
Brain Injuries - etiology
Brain Injuries - prevention & control
Brain Ischemia - diagnosis
Brain Ischemia - etiology
Brain Ischemia - prevention & control
Cytoprotection
Disease Models, Animal
hemostasis
Humans
Intracranial Thrombosis - diagnosis
Intracranial Thrombosis - etiology
Intracranial Thrombosis - prevention & control
Metalloendopeptidases - deficiency
Metalloendopeptidases - genetics
Mice, Inbred C57BL
Mice, Knockout
Neuroprotective Agents - pharmacology
Recombinant Proteins - pharmacology
subarachnoid hemorrhage
Subarachnoid Hemorrhage - complications
thrombosis
Time Factors
von Willebrand factor
thrombosis
hemostasis
subarachnoid hemorrhage
von Willebrand factor
ADAMTS13 protein, human
ISSN:1538-7933, 1538-7836, 1538-7836
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Summary:Summary 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 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.
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ISSN:1538-7933
1538-7836
1538-7836
DOI:10.1111/jth.12574