Nuffield Department of Surgical Sciences, Oxford Transplant Centre, Oxford, United Kingdom.
Oxford University NHS Foundation Trust, Oxford, United Kingdom.
Transplantation. 2024 Apr 1;108(4):923-929. doi: 10.1097/TP.0000000000004900. Epub 2024 Jan 9.
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.
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.
A cohort of 27 donors with brain death duration between 10 and 30 h 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.
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.
实体器官移植是治疗终末期器官衰竭的一种具有成本效益的治疗方法。脑死亡后的器官捐献是移植器官的重要来源。关于脑损伤或供者管理对移植物的影响的数据有限。共识观点一直认为，脑死亡会产生一个逐渐促炎的环境。我们旨在研究在一组因颅内出血而没有任何其他全身炎症源导致脑死亡的供者中，一系列细胞因子随时间的变化。
使用英国器官捐赠质量生物银行定义了一个供者队列。从入院到器官恢复，测量参与促炎和脑损伤途径的蛋白质（肿瘤坏死因子-α、白细胞介素-6、补体 C5a、神经元特异性烯醇化酶和神经胶质纤维酸性蛋白）的血清水平。采用移动中位数分析来组合供者轨迹并描绘时间过程。
创建了一个脑死亡时间在 10 至 30 小时之间的 27 名供者队列，其中 24 名供者参与了时间过程分析。我们在整个供者管理期间没有观察到肿瘤坏死因子-α或白细胞介素-6的增加。神经元损伤标志物和补体 C5a 从入院到器官恢复一直很高，而神经胶质纤维酸性蛋白在脑死亡得到确认时升高。
我们没有发现随着脑死亡时间的延长促炎介质逐渐升高的证据，这对逐渐促炎环境的假设提出了质疑。此外，当逻辑或伦理考虑限制样本可用性时，所提出的方法允许我们研究时间顺序的变化，并确定生物标志物或靶向途径。
