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 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. −/− −/− −/− −/− −/− −/− −/− −/− −/− −/−
Journal of Thrombosis and Haemostasis
Digital Object Identifier (DOI)
Wan, H.; Wang, Y.; Ai, J.; Brathwaite, S.; Ni, H.; Macdonald, R. L.; Hol, E. M.; Meijers, J. C.M.; and Vergouwen, M. D.I., "Role of von Willebrand factor and ADAMTS-13 in early brain injury after experimental subarachnoid hemorrhage" (2018). Neurobiology. 975.