Role of von Willebrand Factor and ADAMTS13 in early brain injury after experimental subarachnoid hemorrhage

H Wan, Y Wang, J Ai, S Brathwaite, H Ni, R L Macdonald, E M Hol, J.C.M. Meijers, Mervyn D I Vergouwen

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Abstract

BACKGROUND: Early brain injury is an important determinant of poor functional outcome and case-fatality after aneurysmal subarachnoid hemorrhage (SAH) and associated with early platelet aggregation. No treatment exists for early brain injury after SAH. We investigated if von Willebrand Factor (VWF) is involved in the pathogenesis of early brain injury, and if ultra-early treatment with recombinant ADAMTS13 (rADAMTS13) 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), ADAMTS13-/- (n=23), and C57BL/6J treated with rADAMTS13 (n=26). Mice were sacrificed at 2 hours post-SAH. Primary outcome measures were microglial activation (Iba-1 surface area) and neuronal injury (number of cleaved caspase-3 positive neurons).

RESULTS: Compared with controls, microglial activation was decreased in VWF-/- mice (mean difference -20.0%; 95% CI: -4.0% to -38.6%), increased in ADAMTS13-/- mice (mean difference +34.0%; 95% CI: 16.2% to 51.7%), and decreased in rADAMTS13 treated mice (mean difference -22.1%; 95% CI: -3.4% to -39.1%). Compared with controls (185 neurons [IQR 133-353]), neuronal injury in the cerebral cortex was decreased in VWF-/- mice (63 neurons [IQR 25-78]), not changed in ADAMTS13-/- mice (53 neurons [IQR 26-221]), and reduced in rADAMTS13 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 rADAMTS13 as a treatment option for early brain injury after SAH. This article is protected by copyright. All rights reserved.

Original languageEnglish
Pages (from-to)1413-1422
JournalJournal of Thrombosis and Haemostasis
Volume16
DOIs
Publication statusPublished - 2018

Keywords

  • Journal Article

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