Extracellular Vesicles in Acute Stroke Diagnostics
Abstract
:1. Introduction
2. Stroke Pathophysiology and Current Treatment
3. Current Stroke Diagnostics
4. Circulating Brain Biomarkers
5. Extracellular Vesicles
Extracellular Vesicles in CNS Pathology
6. EV Isolation and Characterization
7. Extracellular Vesicles in Stroke Diagnostics
8. EV-Derived miRNA in Stroke Diagnostics
9. Conclusions
Funding
Conflicts of Interest
References
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Disease | Results | Origin of EVs | Analysis Method | Patients/Controls | Time Since Onset | Ref. |
---|---|---|---|---|---|---|
AIS—minor (NIHSS < 5) and moderate-severe (NIHSS ≥ 5) | Endothelial cell EVs are linked to severity, lesion volume and outcome of AIS. | Endothelial cell | Flow cytometry | 20 minor stroke 21 moderate–severe stroke/23 age-matched controls | 37 h on avg. | Simak et al. [73] |
AIS | AIS increases EV shedding from blood and vascular compartment cell and neural precursor cell | Endothelial cells, Platelets, erythrocytes, Leukocytes, monocytes lymphocytes and Neural precursor cells | Flow cytometry | 44 AIS/44 controls (age-matched, high cardiovascular risk subjects—no documented vascular disease) | Max 48 h | Chiva-Blanch et al. [67] |
AIS (LAA and cSVD) | Platelet EVs are elevated in all groups, compared with control | Platelets | Flow cytometry | 112 AIS incl. LAA and cSVD stroke/35 controls | Max 48 h | Chen et al. [66] |
AIS (LVO and cSVD) | Platelet EVs are significantly elevated in LVO and cSVD | Platelets | ELISA | 34 cSVD stroke, 41 LVO/61 patients with no apparent cerebral vascular lesions | Max 24 h | Kuriyama et al. [70] |
ICH | The EVs show a distinct temporal profiling depending on their origin. | Endothelial cells, erythrocytes, neutrophils | Flow cytometry | 22 ICH/13 controls | Max 48 h | Sanborn et al. [72] |
ICH | Annexin V positive EVs are elevated in ICH compared to controls at admission | Undetermined | Pro-thrombinase assay | 38 ICH/10 controls | Max 8.5 h | Huang et al. [75] |
ICH | Increase in endothelial, leucocyte and erythrocyte EVs (not platelet) | Endothelial cells, leucocytes erythrocytes | Flow cytometry | 20 ICH/22 controls | Max 48 h | Lackner et al. [76] |
ICH | Annexin V positive EVs are elevated in ICH compared to controls at admission | Undetermined | Pro-thrombinase assay | 86 ICH/30 controls | Max 6 h | Dong et al. [77] |
Stroke Type | miRNA | Expression in Stroke | Source | Analysis | Patients/Controls | Time from Onset | Ref. |
---|---|---|---|---|---|---|---|
AIS (NIHSS: 8) | miR-134 | Upregulated | Serum | ExoQuickexosome isolation, qRT-PCR | 50 AIS/50 controls | Max 24 h | Zhou et al. [82] |
AIS (NIHSS: 6) | miR-21-5 p and 30a-5p | Upregulated in hyper acute phase | Plasma | QIAGEN exoRNeasy, NTA, Flow cytometry, qRT-PCR | 143 AIS/24 non-stroke controls | Max 6 h | Wang et al. [83] |
AIS (NIHSS: N/A) | miR-422a | Upregulated | Plasma | qRT-PCR | 55 AIS/25 age- and sex-matched controls | 1–3 days | Li et al. [84] |
AIS (NIHSS: 3) | miR-223 | Upregulated | Blood | ExoQuickexosome isolation, qRT-PCR | 50 AIS/33 age- and sex-matched controls | 72 h | Chen et al. [85] |
AIS (NIHSS: 8) | miR-9 and miR-124 | Upregulated | Serum | ExoQuickexosome isolation qRT-PCR | 65 AIS/66 non-stroke controls | 16.5 h on avg. | Ji et al. [86] |
AIS&cSVD (NIHSS: 4) | miRNA-17 Family and miR-27b-3p | Upregulated (linked to chronic cSVD) | Serum | Thermo Fisher exosome isolation reagent, qRT-PCR | 139 AIS and chronic cSVD/39 non-stroke (cSVD) patients | 48 h post AIS | Van Kralingen et al. [87] |
ICH, AIS, SAH (NIHSS: N/A) | miR-27b-3p and miR-146b-5p, i.a. | Upregulated | Plasma | QIAGEN exoRNeasy, NGS | 21 AIS, 17 SAH, 19 ICH | Max 24 h | Kalani et al. [88] |
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Stenz, K.T.; Just, J.; Blauenfeldt, R.A.; Drasbek, K.R. Extracellular Vesicles in Acute Stroke Diagnostics. Biomedicines 2020, 8, 248. https://doi.org/10.3390/biomedicines8080248
Stenz KT, Just J, Blauenfeldt RA, Drasbek KR. Extracellular Vesicles in Acute Stroke Diagnostics. Biomedicines. 2020; 8(8):248. https://doi.org/10.3390/biomedicines8080248
Chicago/Turabian StyleStenz, Katrine Tang, Jesper Just, Rolf Ankerlund Blauenfeldt, and Kim Ryun Drasbek. 2020. "Extracellular Vesicles in Acute Stroke Diagnostics" Biomedicines 8, no. 8: 248. https://doi.org/10.3390/biomedicines8080248