Donation after brain death (BD) remains an important source of transplanted organs worldwide and it has been shown that BD causes a hostile environment with a systemic pro-inflammatory, coagulatory response and injury to the grafts-to-be. Recent UK transplant registry analysis demonstrated that a prolonged duration of BD was not associated with worse outcome for abdominal organ transplantation (Boffa, 2017). Indeed, there might be a benefit for longer donor management in some transplanted organs as cytoprotective proteins were found counteracting BD related injury. The underlying mechanisms have however not been studied in detail. The period of donor management thus offers opportunities for targeted therapy. This work aimed to provide a systematic study of changes in neuronal, glial and immunological molecules in serum over time.

Methods

27 donors with severe intracranial haemorrhage (ICH) leading to BD and available serum samples from admission to organ procurement were included. Samples were collected as part of the UK Quality in Organ Donation (QUOD) biobank programme. Pooled samples at four different time points (admission to intensive care, diagnosis of BD, start and end of procurement) were compared. Serum levels of neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP) and interleukin 6 (IL-6) were measured using ELISA.

Results

Serum concentrations of NSE, GFAP and IL-6 were highest at admission to intensive care followed by a decline at time of diagnosis of BD. The serum concentrations of the three markers of cerebral injury did not rise again until procurement. Both GFAP and IL-6 showed an increased serum concentration at the end of procurement with levels of NSE remaining unchanged.

Conclusions

This is the first study demonstrating that the neuroimmunological impact of cerebral injury detected in serum of BD donors following ICH is highest during the initial insult. We show that serum levels of cerebral injury markers do not further increase during the period of donor management. To complete this work we will now study serum changes of NSE, GFAP and IL-6 during different durations of brain death. Understanding neuroimmunological changes following diagnosis of BD might allow to identify novel treatment opportunities for resuscitation and repair of transplanted organs.

References: Boffa et al, Transplantation. 101:S1, August 2017.

CITATION INFORMATION: Bera K., LoFaro M., Huang H., Maslau S., Ploeg R. Unraveling the Neuroimmunological Pathways Surrounding Brain Death: Systematic Study of Clinically Relevant Serum Biomarker Changes during Donor Management from Admission to Procurement Am J Transplant. 2017;17 (suppl 3).

« Back to 2018 American Transplant Congress