Department of Forensic Medicine, Centre for Biostructure Research, Medical University of Warsaw, Poland.
Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology (CePT), Medical University of Warsaw, Poland.
Folia Neuropathol. 2021;59(1):81-90. doi: 10.5114/fn.2021.105137.
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.
创伤性脑损伤 (TBI) 是法医学尸检和神经病理学检查中的常见发现。尽管目前对 TBI 发病机制的关注度前所未有，但仍需要通过使用新型生物标志物来改善其诊断，以促进检测、治疗和预后。最近，生长因子颗粒蛋白前体 (PGRN) 因其神经营养和抗炎活性而引起了广泛关注。尽管已经描述了 PGRN 相关的神经炎症和神经退行性现象，但 PGRN 在 TBI 中的作用尚未得到广泛讨论。本研究旨在确定生物流体中的 PGRN 浓度，并使用免疫组织化学染色检查早期致命性 TBI 个体脑组织中的 PGRN 和 CD68 蛋白表达。该研究使用了 30 例致命性头部损伤病例（TBI 组）和 30 例突发性死亡对照病例（对照组）。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，用抗 PGRN 和抗 CD68 抗体对脑标本进行染色。在我们的研究中，我们观察到 TBI 个体在 TBI 早期阶段血清和尿液中 PGRN 浓度升高。这些变化伴随着额皮质（1-3 层）中 PGRN 表达增加，其中抗 CD68 免疫染色显示弥散性皮质小胶质细胞激活。实施此类检测的可能性为 TBI 诊断和发病机制的研究提供了一种新颖而有趣的工具。此外，鉴于 TBI 个体发生神经退行性疾病的可能性，上述替代生物流体检测可能对非致命性 TBI 病例的临床预后和风险计算有用。
