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Role of von Willebrand factor and ADAMTS‐13 in early brain injury after experimental subarachnoid hemorrhage

ESSENTIALS: von Willebrand Factor (VWF) and ADAMTS13 may affect early injury after subarachnoid hemorrhage (SAH). Early brain injury was assessed in VWF(−/−), ADAMTS13(−/−) and recombinant (r) ADAMTS13 treated mice. VWF(−/−) and rADAMTS13 treated mice had less brain injury than ADAMTS13(−/−) and wil...

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Autores principales: Wan, H., Wang, Y., Ai, J., Brathwaite, S., Ni, H., Macdonald, R.L., Hol, E.M., Meijers, J.C.M., Vergouwen, M.D.I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055612/
https://www.ncbi.nlm.nih.gov/pubmed/29729651
http://dx.doi.org/10.1111/jth.14136
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author Wan, H.
Wang, Y.
Ai, J.
Brathwaite, S.
Ni, H.
Macdonald, R.L.
Hol, E.M.
Meijers, J.C.M.
Vergouwen, M.D.I.
author_facet Wan, H.
Wang, Y.
Ai, J.
Brathwaite, S.
Ni, H.
Macdonald, R.L.
Hol, E.M.
Meijers, J.C.M.
Vergouwen, M.D.I.
author_sort Wan, H.
collection PubMed
description ESSENTIALS: von Willebrand Factor (VWF) and ADAMTS13 may affect early injury after subarachnoid hemorrhage (SAH). Early brain injury was assessed in VWF(−/−), ADAMTS13(−/−) and recombinant (r) ADAMTS13 treated mice. VWF(−/−) and rADAMTS13 treated mice had less brain injury than ADAMTS13(−/−) and wild‐type mice. Early administration of rADAMTS13 may improve outcome after SAH by reducing early brain injury. SUMMARY: BACKGROUND: Early brain injury is an important determinant of poor functional outcome and case fatality after aneurysmal subarachnoid hemorrhage (SAH), and is associated with early platelet aggregation. No treatment exists for early brain injury after SAH. We investigated whether von Willebrand factor (VWF) is involved in the pathogenesis of early brain injury, and whether ultra‐early treatment with recombinant ADAMTS‐13 (rADAMTS‐13) reduces early brain injury after experimental SAH. METHODS: Experimental SAH in mice was induced by prechiasmatic injection of non‐anticoagulated blood from a littermate. The following experimental SAH groups were investigated: C57BL/6J control (n = 21), VWF (−/−) (n = 25), ADAMTS‐13(−/−) (n = 23), and C57BL/6J treated with rADAMTS‐13 (n = 26). Mice were killed at 2 h after SAH. Primary outcome measures were microglial activation (IBA‐1 surface area) and neuronal injury (number of cleaved caspase‐3‐positive neurons). RESULTS: As compared with controls, microglial activation was decreased in VWF (−/−) mice (mean difference of − 20.0%, 95% confidence interval [CI] − 4.0% to − 38.6%), increased in ADAMTS‐13(−/−) mice (mean difference of + 34.0%, 95% CI 16.2–51.7%), and decreased in rADAMTS‐13‐treated mice (mean difference of − 22.1%, 95% CI − 3.4% to − 39.1%). As compared with controls (185 neurons, interquartile range [IQR] 133–353), neuronal injury in the cerebral cortex was decreased in VWF (−/−) mice (63 neurons, IQR 25–78), not changed in ADAMTS‐13(−/−) mice (53 neurons, IQR 26–221), and reduced in rADAMTS‐13‐treated mice (45 neurons, IQR 9–115). CONCLUSIONS: Our findings suggest that VWF is involved in the pathogenesis of early brain injury, and support the further study of rADAMTS‐13 as a treatment option for early brain injury after SAH.
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spelling pubmed-60556122018-07-23 Role of von Willebrand factor and ADAMTS‐13 in early brain injury after experimental subarachnoid hemorrhage Wan, H. Wang, Y. Ai, J. Brathwaite, S. Ni, H. Macdonald, R.L. Hol, E.M. Meijers, J.C.M. Vergouwen, M.D.I. J Thromb Haemost VASCULAR BIOLOGY ESSENTIALS: von Willebrand Factor (VWF) and ADAMTS13 may affect early injury after subarachnoid hemorrhage (SAH). Early brain injury was assessed in VWF(−/−), ADAMTS13(−/−) and recombinant (r) ADAMTS13 treated mice. VWF(−/−) and rADAMTS13 treated mice had less brain injury than ADAMTS13(−/−) and wild‐type mice. Early administration of rADAMTS13 may improve outcome after SAH by reducing early brain injury. SUMMARY: BACKGROUND: Early brain injury is an important determinant of poor functional outcome and case fatality after aneurysmal subarachnoid hemorrhage (SAH), and is associated with early platelet aggregation. No treatment exists for early brain injury after SAH. We investigated whether von Willebrand factor (VWF) is involved in the pathogenesis of early brain injury, and whether ultra‐early treatment with recombinant ADAMTS‐13 (rADAMTS‐13) reduces early brain injury after experimental SAH. METHODS: Experimental SAH in mice was induced by prechiasmatic injection of non‐anticoagulated blood from a littermate. The following experimental SAH groups were investigated: C57BL/6J control (n = 21), VWF (−/−) (n = 25), ADAMTS‐13(−/−) (n = 23), and C57BL/6J treated with rADAMTS‐13 (n = 26). Mice were killed at 2 h after SAH. Primary outcome measures were microglial activation (IBA‐1 surface area) and neuronal injury (number of cleaved caspase‐3‐positive neurons). RESULTS: As compared with controls, microglial activation was decreased in VWF (−/−) mice (mean difference of − 20.0%, 95% confidence interval [CI] − 4.0% to − 38.6%), increased in ADAMTS‐13(−/−) mice (mean difference of + 34.0%, 95% CI 16.2–51.7%), and decreased in rADAMTS‐13‐treated mice (mean difference of − 22.1%, 95% CI − 3.4% to − 39.1%). As compared with controls (185 neurons, interquartile range [IQR] 133–353), neuronal injury in the cerebral cortex was decreased in VWF (−/−) mice (63 neurons, IQR 25–78), not changed in ADAMTS‐13(−/−) mice (53 neurons, IQR 26–221), and reduced in rADAMTS‐13‐treated mice (45 neurons, IQR 9–115). CONCLUSIONS: Our findings suggest that VWF is involved in the pathogenesis of early brain injury, and support the further study of rADAMTS‐13 as a treatment option for early brain injury after SAH. John Wiley and Sons Inc. 2018-06-08 2018-07 /pmc/articles/PMC6055612/ /pubmed/29729651 http://dx.doi.org/10.1111/jth.14136 Text en © 2018 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals, Inc. on behalf of International Society on Thrombosis and Haemostasis. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle VASCULAR BIOLOGY
Wan, H.
Wang, Y.
Ai, J.
Brathwaite, S.
Ni, H.
Macdonald, R.L.
Hol, E.M.
Meijers, J.C.M.
Vergouwen, M.D.I.
Role of von Willebrand factor and ADAMTS‐13 in early brain injury after experimental subarachnoid hemorrhage
title Role of von Willebrand factor and ADAMTS‐13 in early brain injury after experimental subarachnoid hemorrhage
title_full Role of von Willebrand factor and ADAMTS‐13 in early brain injury after experimental subarachnoid hemorrhage
title_fullStr Role of von Willebrand factor and ADAMTS‐13 in early brain injury after experimental subarachnoid hemorrhage
title_full_unstemmed Role of von Willebrand factor and ADAMTS‐13 in early brain injury after experimental subarachnoid hemorrhage
title_short Role of von Willebrand factor and ADAMTS‐13 in early brain injury after experimental subarachnoid hemorrhage
title_sort role of von willebrand factor and adamts‐13 in early brain injury after experimental subarachnoid hemorrhage
topic VASCULAR BIOLOGY
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6055612/
https://www.ncbi.nlm.nih.gov/pubmed/29729651
http://dx.doi.org/10.1111/jth.14136
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