Role of von Willebrand factor and ADAMTS-13 in early brain injury after
experimental subarachnoid hemorrhage
#MMPMID29729651
Wan H
; Wang Y
; Ai J
; Brathwaite S
; Ni H
; Macdonald RL
; Hol EM
; Meijers JCM
; Vergouwen MDI
J Thromb Haemost
2018[Jul]; 16
(7
): 1413-1422
PMID29729651
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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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