TY - JOUR
T1 - Serum amyloid A and mitochondrial DNA in extracellular vesicles are novel markers for detecting traumatic brain injury in a mouse model
AU - Tang, Tony Z.
AU - Zhao, Yingxin
AU - Agarwal, Deepesh
AU - Tharzeen, Aabila
AU - Patrikeev, Igor
AU - Zhang, Yuanyi
AU - DeJesus, Jana
AU - Bossmann, Stefan H.
AU - Natarajan, Balasubramaniam
AU - Motamedi, Massoud
AU - Szczesny, Bartosz
N1 - Publisher Copyright:
© 2024
PY - 2024/2/16
Y1 - 2024/2/16
N2 - 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.
AB - 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.
KW - Cellular neuroscience
KW - Molecular neuroscience
UR - http://www.scopus.com/inward/record.url?scp=85183492867&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85183492867&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2024.108932
DO - 10.1016/j.isci.2024.108932
M3 - Article
AN - SCOPUS:85183492867
SN - 2589-0042
VL - 27
JO - iScience
JF - iScience
IS - 2
M1 - 108932
ER -