Plasma Rich in Growth Factors (PRGF) Disrupt the Blood-Brain Barrier Integrity and Elevate Amyloid Pathology in the Brains of 5XFAD Mice
Alzheimer’s disease (AD) is the most common neurodegenerative disorder affecting 5.4 million people in the United States. Currently approved pharmacologic interventions for AD are limited to symptomatic improvement, not affecting the underlying pathology. Therefore, the search for novel th...
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| Format: | Article |
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MDPI AG
2019-03-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/20/6/1489 |
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| author | Quoc-Viet Duong Margia L. Kintzing William E. Kintzing Ihab M. Abdallah Andrew D. Brannen Amal Kaddoumi |
| author_facet | Quoc-Viet Duong Margia L. Kintzing William E. Kintzing Ihab M. Abdallah Andrew D. Brannen Amal Kaddoumi |
| author_sort | Quoc-Viet Duong |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is the most common neurodegenerative disorder affecting 5.4 million people in the United States. Currently approved pharmacologic interventions for AD are limited to symptomatic improvement, not affecting the underlying pathology. Therefore, the search for novel therapeutic strategies is ongoing. A hallmark of AD is the compromised blood-brain barrier (BBB); thus, developing drugs that target the BBB to enhance its integrity and function could be a novel approach to prevent and/or treat AD. Previous evidence has shown the beneficial effects of growth factors in the treatment of AD pathology. Based on reported positive results obtained with the product Endoret<sup>®</sup>, the objective of this study was to investigate the effect of plasma rich in growth factors (PRGF) on the BBB integrity and function, initially in a cell-based BBB model and in 5x Familial Alzheimer’s Disease (5xFAD) mice. Our results showed that while PRGF demonstrated a positive effect in the cell-based BBB model with the enhanced integrity and function of the model, the in-vivo findings showed that PRGF exacerbated amyloid pathology in 5xFAD brains. At 10 and 100% doses, PRGF increased amyloid deposition associated with increased apoptosis and neuroinflammation. In conclusion, our results suggest PRGF may not provide beneficial effects against AD and the consideration to utilize growth factors should further be investigated. |
| first_indexed | 2024-04-13T01:18:41Z |
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| id | doaj.art-64a7868a035e4ea88b4c0b13109b3649 |
| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-13T01:18:41Z |
| publishDate | 2019-03-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-64a7868a035e4ea88b4c0b13109b36492022-12-22T03:08:49ZengMDPI AGInternational Journal of Molecular Sciences1422-00672019-03-01206148910.3390/ijms20061489ijms20061489Plasma Rich in Growth Factors (PRGF) Disrupt the Blood-Brain Barrier Integrity and Elevate Amyloid Pathology in the Brains of 5XFAD MiceQuoc-Viet Duong0Margia L. Kintzing1William E. Kintzing2Ihab M. Abdallah3Andrew D. Brannen4Amal Kaddoumi5Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USAHealth Science Center, LSU Department of Family Medicine, Shreveport, LA 71103, USAHealth Science Center, LSU Department of Family Medicine, Shreveport, LA 71103, USADepartment of Drug Discovery and Development, Harrison School of Pharmacy, Pharmacy Research Building, Auburn University, Auburn, AL 36849, USADepartment of Drug Discovery and Development, Harrison School of Pharmacy, Pharmacy Research Building, Auburn University, Auburn, AL 36849, USADepartment of Drug Discovery and Development, Harrison School of Pharmacy, Pharmacy Research Building, Auburn University, Auburn, AL 36849, USAAlzheimer’s disease (AD) is the most common neurodegenerative disorder affecting 5.4 million people in the United States. Currently approved pharmacologic interventions for AD are limited to symptomatic improvement, not affecting the underlying pathology. Therefore, the search for novel therapeutic strategies is ongoing. A hallmark of AD is the compromised blood-brain barrier (BBB); thus, developing drugs that target the BBB to enhance its integrity and function could be a novel approach to prevent and/or treat AD. Previous evidence has shown the beneficial effects of growth factors in the treatment of AD pathology. Based on reported positive results obtained with the product Endoret<sup>®</sup>, the objective of this study was to investigate the effect of plasma rich in growth factors (PRGF) on the BBB integrity and function, initially in a cell-based BBB model and in 5x Familial Alzheimer’s Disease (5xFAD) mice. Our results showed that while PRGF demonstrated a positive effect in the cell-based BBB model with the enhanced integrity and function of the model, the in-vivo findings showed that PRGF exacerbated amyloid pathology in 5xFAD brains. At 10 and 100% doses, PRGF increased amyloid deposition associated with increased apoptosis and neuroinflammation. In conclusion, our results suggest PRGF may not provide beneficial effects against AD and the consideration to utilize growth factors should further be investigated.https://www.mdpi.com/1422-0067/20/6/1489blood-brain barrieramyloid-β clearancebrain endothelial cellsvascular endothelial growth factorplasma rich growth factors |
| spellingShingle | Quoc-Viet Duong Margia L. Kintzing William E. Kintzing Ihab M. Abdallah Andrew D. Brannen Amal Kaddoumi 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 blood-brain barrier amyloid-β clearance brain endothelial cells vascular endothelial growth factor plasma rich growth factors |
| title | Plasma Rich in Growth Factors (PRGF) Disrupt the Blood-Brain Barrier Integrity and Elevate Amyloid Pathology in the Brains of 5XFAD Mice |
| title_full | Plasma Rich in Growth Factors (PRGF) Disrupt the Blood-Brain Barrier Integrity and Elevate Amyloid Pathology in the Brains of 5XFAD Mice |
| title_fullStr | Plasma Rich in Growth Factors (PRGF) Disrupt the Blood-Brain Barrier Integrity and Elevate Amyloid Pathology in the Brains of 5XFAD Mice |
| title_full_unstemmed | Plasma Rich in Growth Factors (PRGF) Disrupt the Blood-Brain Barrier Integrity and Elevate Amyloid Pathology in the Brains of 5XFAD Mice |
| title_short | Plasma Rich in Growth Factors (PRGF) Disrupt the Blood-Brain Barrier Integrity and Elevate Amyloid Pathology in the Brains of 5XFAD Mice |
| title_sort | plasma rich in growth factors prgf disrupt the blood brain barrier integrity and elevate amyloid pathology in the brains of 5xfad mice |
| topic | blood-brain barrier amyloid-β clearance brain endothelial cells vascular endothelial growth factor plasma rich growth factors |
| url | https://www.mdpi.com/1422-0067/20/6/1489 |
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