Department of Anatomy, University of Otago, Dunedin, New Zealand.
Institute of Legal Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Int J Legal Med. 2021 Nov;135(6):2323-2333. doi: 10.1007/s00414-021-02568-1. Epub 2021 Jun 11.
Glial fibrillary acidic protein (GFAP) is a well-established astrocytic biomarker for the diagnosis, monitoring and outcome prediction of traumatic brain injury (TBI). Few studies stated an accumulation of neuronal GFAP that was observed in various brain pathologies, including traumatic brain injuries. As the neuronal immunopositivity for GFAP in Alzheimer patients was shown to cross-react with non-GFAP epitopes, the neuronal immunopositivity for GFAP in TBI patients should be challenged. In this study, cerebral and cerebellar tissues of 52 TBI fatalities and 17 controls were screened for immunopositivity for GFAP in neurons by means of immunohistochemistry and immunofluorescence. The results revealed that neuronal immunopositivity for GFAP is most likely a staining artefact as negative controls also revealed neuronal GFAP staining. However, the phenomenon was twice as frequent for TBI fatalities compared to non-TBI control cases (12 vs. 6%). Neuronal GFAP staining was observed in the pericontusional zone and the ipsilateral hippocampus, but was absent in the contralateral cortex of TBI cases. Immunopositivity for GFAP was significantly correlated with the survival time (r = 0.306, P = 0.015), but no correlations were found with age at death, sex nor the post-mortem interval in TBI fatalities. This study provides evidence that the TBI-associated neuronal immunopositivity for GFAP is indeed a staining artefact. However, an absence post-traumatic neuronal GFAP cannot readily be assumed. Regardless of the particular mechanism, this study revealed that the artefact/potential neuronal immunopositivity for GFAP is a global, rather than a regional brain phenomenon and might be useful for minimum TBI survival time determinations, if certain exclusion criteria are strictly respected.
胶质纤维酸性蛋白(GFAP)是一种已被广泛认可的星形胶质细胞生物标志物,可用于创伤性脑损伤(TBI)的诊断、监测和预后预测。有少数研究表明,在包括创伤性脑损伤在内的各种脑病理中,存在神经元 GFAP 的积累。由于阿尔茨海默病患者的神经元 GFAP 免疫阳性反应与非 GFAP 表位发生交叉反应,因此需要对 TBI 患者的神经元 GFAP 免疫阳性反应进行挑战。在这项研究中,通过免疫组织化学和免疫荧光法,对 52 例 TBI 死亡病例和 17 例对照的大脑和小脑组织进行了神经元 GFAP 免疫阳性反应的筛选。结果表明,神经元 GFAP 免疫阳性反应很可能是一种染色假象,因为阴性对照也显示出神经元 GFAP 染色。然而,与非 TBI 对照组相比,TBI 死亡病例中这种现象更为常见(12 例对 6 例)。神经元 GFAP 染色见于脑挫伤区和同侧海马,但 TBI 病例的对侧皮质中未见染色。GFAP 免疫阳性反应与生存时间显著相关(r=0.306,P=0.015),但在 TBI 死亡病例中,与死亡年龄、性别或死后间隔时间均无相关性。本研究提供了证据表明,与 TBI 相关的神经元 GFAP 免疫阳性反应确实是一种染色假象。然而,不能轻易地假设创伤后神经元 GFAP 不存在。无论特定的机制如何,本研究表明,这种假阳性/潜在的神经元 GFAP 免疫阳性反应是一种全局性的,而不是区域性的大脑现象,如果严格遵守某些排除标准,它可能对最小 TBI 生存时间的确定有用。