Plasma Rich in Growth Factors (PRGF) Disrupt the Blood-Brain Barrier Integrity and Elevate Amyloid Pathology in the Brains of 5XFAD Mice.

Autor: Duong QV; Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, Monroe, LA 71201, USA. duongqa@warhawks.ulm.edu., Kintzing ML; Health Science Center, LSU Department of Family Medicine, Shreveport, LA 71103, USA. plkintzing@att.net., Kintzing WE; Health Science Center, LSU Department of Family Medicine, Shreveport, LA 71103, USA. Wkintz@lsuhsc.edu., Abdallah IM; Department of Drug Discovery and Development, Harrison School of Pharmacy, Pharmacy Research Building, Auburn University, Auburn, AL 36849, USA. iza0012@tigermail.auburn.edu., Brannen AD; Department of Drug Discovery and Development, Harrison School of Pharmacy, Pharmacy Research Building, Auburn University, Auburn, AL 36849, USA. adb0009@auburn.edu., Kaddoumi A; Department of Drug Discovery and Development, Harrison School of Pharmacy, Pharmacy Research Building, Auburn University, Auburn, AL 36849, USA. kaddoumi@auburn.edu.
Jazyk: angličtina
Zdroj: International journal of molecular sciences [Int J Mol Sci] 2019 Mar 25; Vol. 20 (6). Date of Electronic Publication: 2019 Mar 25.
DOI: 10.3390/ijms20061489
Abstrakt: 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 ® , 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.
Databáze: MEDLINE
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