Traumatic brain injury (TBI) is a frequent finding during forensic autopsies and neuropathological examinations in medico-legal practices. Despite the unprecedented attention currently focused on TBI pathogenesis, there is a need to improve its diagnostics through the use of novel biomarkers to facilitate detection, treatment, and prognosis. Recently, growth factor progranulin (PGRN) has attracted significant attention because of its neurotrophic and anti-inflammatory activities. The role of PGRN in TBI has not been widely discussed, although PGRN-related neuroinflammatory and neurodegenerative phenomena have been described. The aim of this study was to identify PGRN concentration levels in biofluids and examine PGRN and CD68 protein expression in brain tissue using immunohistochemical staining in individuals with fatal TBI in its early phase. The study was performed using cases (n = 30) of fatal head injury and control cases (n = 30) of sudden death. The serum and urine were collected within ~24 h after death and compared using the ELISA test, where brain specimens were stained with anti-PGRN and anti-CD68 antibodies. In our study, we observed elevated concentration levels of PGRN in the serum and urine of TBI individuals in the early phase of TBI. These changes were accompanied by increased expression of PGRN in the frontal cortex (1st-3rd layers), in which anti-CD68 immunostaining revealed disseminated cortical microglia activation. The possible implementation of performing such assays offers a novel and interesting tool for investigation and research regarding TBI diagnosis and pathogenesis. Furthermore, the above-mentioned surrogate biofluid assays may be useful in clinical prognosis and risk calculation of non-fatal cases of TBI, considering the development of neurodegenerative conditions of TBI individuals.

中文翻译：

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血清和尿液中颗粒蛋白前体 (PGRN) 水平升高作为外伤性脑损伤早期小胶质细胞激活的预测指标：与神经退行性疾病发展的进一步联系

外伤性脑损伤 (TBI) 是法医尸体解剖和法医实践中的神经病理学检查中的常见发现。尽管目前对 TBI 发病机制的关注前所未有，但仍需要通过使用新型生物标志物来促进检测、治疗和预后来改进其诊断。最近，生长因子颗粒蛋白前体 (PGRN) 由于其神经营养和抗炎活性而引起了极大的关注。PGRN 在 TBI 中的作用尚未得到广泛讨论，尽管已描述了与 PGRN 相关的神经炎症和神经退行性现象。本研究的目的是确定生物体液中的 PGRN 浓度水平，并使用免疫组织化学染色检查早期致命性 TBI 个体的脑组织中 PGRN 和 CD68 蛋白的表达。该研究使用致命性头部损伤病例 (n = 30) 和猝死对照病例 (n = 30) 进行。在死后约 24 小时内收集血清和尿液，并使用 ELISA 测试进行比较，其中脑标本用抗 PGRN 和抗 CD68 抗体染色。在我们的研究中，我们观察到 TBI 早期患者血清和尿液中 PGRN 的浓度水平升高。这些变化伴随着额叶皮层（第 1-3 层）中 PGRN 的表达增加，其中抗 CD68 免疫染色显示播散性皮层小胶质细胞活化。执行此类检测的可能实施为有关 TBI 诊断和发病机制的调查和研究提供了一种新颖有趣的工具。此外，