Serum amyloid A and mitochondrial DNA in extracellular vesicles are novel markers for detecting traumatic brain injury in a mouse model

• Published in: iScience 2024-02, Vol.27 (2), p.108932-108932, Article 108932
• Main Authors: Tang, Tony Z., Zhao, Yingxin, Agarwal, Deepesh, Tharzeen, Aabila, Patrikeev, Igor, Zhang, Yuanyi, DeJesus, Jana, Bossmann, Stefan H., Natarajan, Balasubramaniam, Motamedi, Massoud, Szczesny, Bartosz
• Format: Article
• Language: English
• Subjects: Cellular neuroscience; Molecular neuroscience
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2024.108932

This study investigates the potential use of circulating extracellular vesicles’ (EVs) DNA and protein content as biomarkers for traumatic brain injury (TBI) in a mouse model. Despite an overall decrease in EVs count during the acute phase, there was an increased presence of exosomes (CD63+ EVs) during acute and an increase in microvesicles derived from microglia/macrophages (CD11b+ EVs) and astrocytes (ACSA-2+ EVs) in post-acute TBI phases, respectively. Notably, mtDNA exhibited an immediate elevation post-injury. Neuronal (NFL) and microglial (Iba1) markers increased in the acute, while the astrocyte marker (GFAP) increased in post-acute TBI phases. Novel protein biomarkers (SAA, Hp, VWF, CFD, CBG) specific to different TBI phases were also identified. Biostatistical modeling and machine learning identified mtDNA and SAA as decisive markers for TBI detection. These findings emphasize the importance of profiling EVs’ content and their dynamic release as an innovative diagnostic approach for TBI in liquid biopsies. [Display omitted] •TBI changes quantity and size of circulating EVs in blood•Distinct release of exosomes, and EVs from microglia and astrocytes•EVs display a distinctive pattern of neuronal, astrocyte, and microglia markers•Serum amyloid A and mitochondrial DNA are novel markers of the acute TBI phase Molecular neuroscience; Cellular neuroscience