Table 3 EVs are an emerging class diagnostic markers for TBI and associated complicationsa
EV Sources: Cell type/Tissue/species | Method of measurement | Tested components of EV | Sampling time point | Main findings | Ref |
|---|---|---|---|---|---|
Endothelial, platelet, and leukocyte/plasma/human | Flow cytometry | •TF •P-selection | 6,12,24,48 and 72 h post-injury | MP counts in cerebral vein samples, regardless of cell origin, were higher in TBI cases compared with healthy groups; and MP counts decreased sharply from high levels shortly after TBI to slightly higher levels 72 h later | M.Nekludov et al. [54] |
EV in circulating blood /Plasma/human | Paramagnetic bead-based enzyme-linked immunosorbent assay | Protein quantification | years post injury | The levels of plasma EV and NfL were significantly increased in patients with repeated mild TBI; Even years after injury, the increase was greatest in patients with chronic post-concussive syndrome, post-traumatic stress disorder, and depression symptoms | Guedes VA et al. [171] |
BDEVs/plasm/mouse and human | •RNA sequencing •Machine learning algorithms | miRNA | 1 h after single or multiple injuries, 0.4–120 h after injury(clinical samples) | Machine learning algorithms processing miRNAs in brain-derived EVs can detect various injury types and characteristics of TBI, reflecting the heterogeneity of human TBI injury and recovery more accurately than traditional diagnosis | Ko J et al. [172] |
EV in circulating blood /plasm/human | •ELISA •RNA Sequencing | •GFAP •Short noncoding RNA | — | Increased GFAP concentrations in EVs from TBI patients with altered consciousness, as well as differential expression of multiple miRNAs targeting TBI-related pathways, suggest that EVs may be potential carriers of TBI biomarkers | Puffer RC et al. [173] |
Astrocytes/culture medium/ human | Droplet digital PCR | specific subset of miRNAs | 24 h post-IL-1β induced inflammatory stress | Astrocyte-derived EVs express a specific subset of miRNA that may play a potential role in modulating inflammatory responses | Manoshi Gayen et al. [34] |
Neurons/ brain/ Mouse | RNA sequencing | miR-21 | 1–7 days post- injury | As a potential neuron-derived EV cargo, miR-21 may mediate the activation of microglia | Harrison EB et al. [35] |
Brain endothelial cells/ plasma/Mouse | •Flow Cytometry •Electron microscopy | Tight junction proteins | 24 h post-injury | •Brain endothelial cells release eEVs containing TJP and endothelial markers to mediate vascular remodeling after TBI •Detection of brain endothelial-derived EVs provides a novel approach to assess BBB structure and function in trauma and neuroinflammation | Andrews AM et al. [38] |
Neurons and glial cells/ brain, plasma/Mouse | •Flow Cytometry •Electron microscopy | PS and TF on membrane | 0.5,1,3 and 6 h post-injury | •The traumatized brain releases procoagulant BDMPs into the circulation to trigger a disseminated coagulation cascade •The abundance of PS and TF on the membrane surface is responsible for the procoagulant activity of BDMPs | Ye Tian et al. [23] |
Neurons and glial cells/ plasma/ Mouse | •Flow Cytometry •Electron microscopy | CL on mitochondrial membrane | 0.25, 0.5,1,3,7,10,14 days post-injury | •The mtMP is a major subset of BDEVs •Abundant CL on the membrane surface is responsible for mtMPs-triggered coagulation dysfunction after TBI | Zilong Zhao et al. [24] |
EV in circulating blood /plasma/human | RNA sequencing | Specific mRNA and lncRNA | — | Analysis of SEV and LEV cargoes suggests that RNA may serve as novel, readily accessible biomarkers for AD, PD, ALS, and FTD in the future | Sproviero et al. D [47] |