Background. Solid organ transplantation is a cost-effective treatment for end-stage organ failure. Organ donation after
brain death is an important source of transplanted organs. Data are limited on the effects of brain injury or donor management
on grafts. The consensus view has been that brain death creates a progressively ...
Background. Solid organ transplantation is a cost-effective treatment for end-stage organ failure. Organ donation after
brain death is an important source of transplanted organs. Data are limited on the effects of brain injury or donor management
on grafts. The consensus view has been that brain death creates a progressively proinflammatory environment. We aimed
to investigate time-course changes across a range of cytokines in a donation after brain death cohort of donors who died of
intracranial hemorrhage without any other systemic source of inflammation. Methods. A donor cohort was defined using
the UK Quality in Organ Donation biobank. Serum levels of proteins involved in proinflammatory and brain injury pathways
(tumor necrosis factor-alpha, interleukin-6, complement C5a, neuron-specific enolase, and glial fibrillary acidic protein) were
measured from admission to organ recovery. Moving median analysis was used to combine donor trajectories and delineate
a time-course. Results. A cohort of 27 donors with brain death duration between 10 and 30h was created, with 24 donors
contributing to the time-course analysis. We observed no increase in tumor necrosis factor-alpha or interleukin-6 throughout
the donor management period. Neuronal injury marker and complement C5a remain high from admission to organ recovery,
whereas glial fibrillary acidic protein rises around the confirmation of brain death. Conclusions. We found no evidence
of a progressive rise of proinflammatory mediators with prolonged duration of brain death, questioning the hypothesis of a
progressively proinflammatory environment. Furthermore, the proposed approach allows us to study chronological changes
and identify biomarkers or target pathways when logistical or ethical considerations limit sample availability.
