Plasma Rich in Growth Factors (PRGF) Disrupt the Blood-Brain Barrier Integrity and Elevate Amyloid Pathology in the Brains of 5XFAD Mice
Abstract
:1. Introduction
2. Results
2.1. Growth Factor Concentrations in Activated Plasma
2.2. PRGF Increased bEnd3 Monolayer Tightness and Aβ42 Transport Across the Cell-Based BBB Model
2.3. VEGF and PRGF Enhanced 125I-Aβ40 Clearance across Mice BBB with Differing Effect on Aβ Brain Load
2.4. VEGF and PRGF modulated BBB tightness in 5xFAD mice brains
2.5. VEGF and PRGF Altered Aβ Levels, Increased Astrocytes Activation and Altered Aβ Major Transport Proteins in 5xFAD Mice Brains
2.6. VEGF and PRGF Reduced Angiogenesis Markers, Increased Apoptosis, and Increased Amyloid Production
2.7. VEGF and PRGF Reduced the Expression of Postsynaptic Density-95 (PSD-95) in 5xFAD Mice Brains
2.8. VEGF and PRGF Treatment Increased Cytokines and Neuroinflammatory Markers in 5xFAD Mice Brains
3. Discussion
4. Materials and Methods
4.1. Plasma Rich Derived Growth Factors Extraction and Quantification
4.2. In-Vitro Cell Culture
4.3. Lucifer Yellow Permeability Assay
4.4. Amyloid-β Transport Across bEnd3 Cell Monolayer
4.5. Animals
4.6. Animal Treatment
4.7. 5xFAD Brain Efflux Index Study
4.8. Isolation of Mouse Brain Microvessels
4.9. Western Blot Analysis
4.10. Immunohistochemistry Analysis
4.11. Amyloid-β Quantification by ELISA
4.12. Cytokine Array
4.13. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AD | Alzheimer’s Disease |
BBB | Blood-Brain Barrier |
Aβ | Amyloid- β |
P-gp | P-glycoprotein |
LRP1 | Low-Density Lipoprotein Receptor Related Protein-1 |
TJs | Tight Junction Proteins |
ZO | Zonula-occludin |
PRGF | Plasma Rich in Growth Factors |
VEGF | Vascular Endothelial Growth Factor |
TGF-β1 | Transforming Growth Factor |
CD | Cluster of Differentiation |
PDGFR | Platelet-Derived Growth Factor Receptor |
APP | Amyloid Precursor Protein |
AKT | Protein Kinase B |
p-AKT | Phosphorylated AKT |
GAPDH | Glyceraldehyde 3-phosphate dehydrogenase |
TNF | Tumor Necrosis Factor |
INF | Interferon |
IL | Interleukin |
IP | Interferon Gamma-Induced Protein 10 |
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Duong, Q.-V.; Kintzing, M.L.; Kintzing, W.E.; Abdallah, I.M.; Brannen, A.D.; Kaddoumi, A. Plasma Rich in Growth Factors (PRGF) Disrupt the Blood-Brain Barrier Integrity and Elevate Amyloid Pathology in the Brains of 5XFAD Mice. Int. J. Mol. Sci. 2019, 20, 1489. https://doi.org/10.3390/ijms20061489
Duong Q-V, Kintzing ML, Kintzing WE, Abdallah IM, Brannen AD, Kaddoumi A. Plasma Rich in Growth Factors (PRGF) Disrupt the Blood-Brain Barrier Integrity and Elevate Amyloid Pathology in the Brains of 5XFAD Mice. International Journal of Molecular Sciences. 2019; 20(6):1489. https://doi.org/10.3390/ijms20061489
Chicago/Turabian StyleDuong, Quoc-Viet, Margia L. Kintzing, William E. Kintzing, Ihab M. Abdallah, Andrew D. Brannen, and Amal Kaddoumi. 2019. "Plasma Rich in Growth Factors (PRGF) Disrupt the Blood-Brain Barrier Integrity and Elevate Amyloid Pathology in the Brains of 5XFAD Mice" International Journal of Molecular Sciences 20, no. 6: 1489. https://doi.org/10.3390/ijms20061489