Preclinical study reveals caADAMTS13 reduces neutrophil inflammation without worsening bleeding in stroke models, indicating potential utility prior to diagnostic brain imaging.
Key Points
To determine whether constitutively active ADAMTS13 (caADAMTS13) is safe in intracerebral haemorrhage and evaluate its therapeutic potential when stroke subtype is unknown prior to hospital imaging.
Tested caADAMTS13 in zebrafish larval and murine intracerebral haemorrhage models.
Administered the treatment during hyperacute (1 hour) and delayed (12 or 24 hours) post-injury timepoints.
Quantified haemorrhage progression, early cerebrovascular von Willebrand factor accumulation (4 hours), and neutrophil infiltration at 24 hours and 7 days.
Neither hyperacute (1 hour) nor delayed (12 or 24 hours) caADAMTS13 administration exacerbated bleeding in zebrafish larval or murine haemorrhage models.
caADAMTS13 did not alter early von Willebrand factor accumulation at 4 hours or acute neutrophil recruitment at 24 hours, but reduced vascular neutrophil deposition by 80% at 7 days post-haemorrhage in mice.
Delayed treatment with caADAMTS13 decreased brain neutrophil recruitment by 37% and brain injury by 32%, significantly improving overall outcomes in zebrafish larvae.