Table 2.
Articles describing the beneficial effect of extracellular vesicle (EV) therapy in status epilepticus (SE) and traumatic brain injury (TBI) models.
| Article | Species | Model | Dose and Time Point | EV Type | What was Measured | Isolation Method | Characterization of EVs | Main Finding |
|---|---|---|---|---|---|---|---|---|
| [82] | rat | controlled cortical impact -induced TBI | 100 µg total proteins, 1 d post-injury | rat MSC EVs | Foot-Fault Test, modified Morris water maze, modified Neurological Severity Score, immunohistochemistry | ExoQuick | Total protein concentration, qNano | EVs improved spatial learning and sensorimotor functional recovery, reduced neuroinflammation and increased the number of newly generated endothelial cells. |
| [83] | rat | controlled cortical impact -induced TBI | 100 µg proteins, 3 × 109 particles, 1 d after injury | human MSC EVs, cultured in 2D and 3D conditions | Modified neurological severity score, foot-fault test, Morris water maze, immunohistochemistry | ExoQuick | Total protein concentration, qNano | EVs enhanced spatial learning, reduced brain inflammation, increased neurogenesis in DG, vascular density and angiogenesis |
| [84] | rat | free -falling method | 100, 250, 500 and 1000 µg/mL, time not mentioned | human exfoliated deciduous teeth stem cell EVs | Basso, Beattie and Bresnahan scores, histopathology and immunofluorescense | ExoQuick | Flow cytometry with CD81, CD63 and CD9, TEM, Western blot with CD9 and CD63 | EVs improved rat motor functional recovery and reduced cortical lesion 2 weeks post-injury |
| [85] | mouse | 1 h post-TBI | human MSC EVs | human MSC EVs | Morris water maze, pattern separation test, immunohistochemistry, cytokines in plasma | Anion exchange column | NTA | EVs rescued pattern separation and spatial learning impairments |
| [86] | swine | computer-controlled cortical impact -induced TBI | 1 × 1013 particles, 9 h, 1 d, 5 d, 9 d, and 13 d post-injury | human MSC EVs | Neurocognitive function test, neurologic severity score (NSS) | Sequential centrifugation | qNano | EV treated animals had better neurological functions first 5 d post-TBI and they completed neurological recovery in shorter time |
| [87] | mouse | controlled cortical impact -induced TBI | EVs from 4 × 106 cells, 2 h post-TBI | endothelial colony-forming cell EVs | Brain water content, beam-walking, corner test, immunofluorescence | Sequential centrifugation | TEM, NTA and Western blot with CD9, CD81 and HSP70 | EVs inhibited PTEN expression, increased AKT expression and reduced Evans blue dye extravasation, brain edema and tight junction degradation |
| [88] | rat | mild controlled cortical impact -induced TBI | 100 µg total proteins, 3 h post-TBI | adipose-derived stem cell EVs | Elevated body swing test, forelimb akinesia, paw grasp, in vivo and ex vivo imaging, immunohistochemistry and RNA sequencing | ExoQuick following magnetic bead capture with CD9, CD63 and CD81 | NTA | MALAT1 containing EVs promoted recovery of function on motor behavior and reduction in cortical brain injury |
| [89] | mouse | pilocarpine-induced SE | 30 µg, approximately 15x10^9 particles, same day and 18 h after SE | human MSC from bone marrow EVs | Object location test, novel object recognition test, pattern separation test, immunostaining, cytokine levels | Anion exchange column | Protein concentration, NTA, anti-inflammatory assay | EVs reduced inflammation in hippocampus, repressed neurodegeneration, aberrant neurogenesis and cognitive and memory impairments |
Abbreviations: MSC = mesenchymal stem cell, NTA = nanoparticle tracking analysis, DG = dentate gyrus, TEM = transmission electron microscopy