Cargando…
Regulation of P-glycoprotein and Breast Cancer Resistance Protein Expression Induced by Focused Ultrasound-Mediated Blood-Brain Barrier Disruption: A Pilot Study
The blood-brain barrier (BBB) controls brain homeostasis; it is formed by vascular endothelial cells that are physically connected by tight junctions (TJs). The BBB expresses efflux transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), which limit the passage of sub...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779754/ https://www.ncbi.nlm.nih.gov/pubmed/36555129 http://dx.doi.org/10.3390/ijms232415488 |
_version_ | 1784856687156396032 |
---|---|
author | Conti, Allegra Geffroy, Francoise Kamimura, Hermes A. S. Novell, Anthony Tournier, Nicolas Mériaux, Sébastien Larrat, Benoit |
author_facet | Conti, Allegra Geffroy, Francoise Kamimura, Hermes A. S. Novell, Anthony Tournier, Nicolas Mériaux, Sébastien Larrat, Benoit |
author_sort | Conti, Allegra |
collection | PubMed |
description | The blood-brain barrier (BBB) controls brain homeostasis; it is formed by vascular endothelial cells that are physically connected by tight junctions (TJs). The BBB expresses efflux transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), which limit the passage of substrate molecules from blood circulation to the brain. Focused ultrasound (FUS) with microbubbles can create a local and reversible detachment of the TJs. However, very little is known about the effect of FUS on the expression of efflux transporters. We investigated the in vivo effects of moderate acoustic pressures on both P-gp and BCRP expression for up to two weeks after sonication. Magnetic resonance-guided FUS was applied in the striatum of 12 rats. P-gp and BCRP expression were determined by immunohistochemistry at 1, 3, 7, and 14 days postFUS. Our results indicate that FUS-induced BBB opening is capable of (i) decreasing P-gp expression up to 3 days after sonication in both the treated and in the contralateral brain regions and is capable of (ii) overexpressing BCRP up to 7 days after FUS in the sonicated regions only. Our findings may help improve FUS-aided drug delivery strategies by considering both the mechanical effect on the TJs and the regulation of P-gp and BCRP. |
format | Online Article Text |
id | pubmed-9779754 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-97797542022-12-23 Regulation of P-glycoprotein and Breast Cancer Resistance Protein Expression Induced by Focused Ultrasound-Mediated Blood-Brain Barrier Disruption: A Pilot Study Conti, Allegra Geffroy, Francoise Kamimura, Hermes A. S. Novell, Anthony Tournier, Nicolas Mériaux, Sébastien Larrat, Benoit Int J Mol Sci Article The blood-brain barrier (BBB) controls brain homeostasis; it is formed by vascular endothelial cells that are physically connected by tight junctions (TJs). The BBB expresses efflux transporters such as P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), which limit the passage of substrate molecules from blood circulation to the brain. Focused ultrasound (FUS) with microbubbles can create a local and reversible detachment of the TJs. However, very little is known about the effect of FUS on the expression of efflux transporters. We investigated the in vivo effects of moderate acoustic pressures on both P-gp and BCRP expression for up to two weeks after sonication. Magnetic resonance-guided FUS was applied in the striatum of 12 rats. P-gp and BCRP expression were determined by immunohistochemistry at 1, 3, 7, and 14 days postFUS. Our results indicate that FUS-induced BBB opening is capable of (i) decreasing P-gp expression up to 3 days after sonication in both the treated and in the contralateral brain regions and is capable of (ii) overexpressing BCRP up to 7 days after FUS in the sonicated regions only. Our findings may help improve FUS-aided drug delivery strategies by considering both the mechanical effect on the TJs and the regulation of P-gp and BCRP. MDPI 2022-12-07 /pmc/articles/PMC9779754/ /pubmed/36555129 http://dx.doi.org/10.3390/ijms232415488 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Conti, Allegra Geffroy, Francoise Kamimura, Hermes A. S. Novell, Anthony Tournier, Nicolas Mériaux, Sébastien Larrat, Benoit Regulation of P-glycoprotein and Breast Cancer Resistance Protein Expression Induced by Focused Ultrasound-Mediated Blood-Brain Barrier Disruption: A Pilot Study |
title | Regulation of P-glycoprotein and Breast Cancer Resistance Protein Expression Induced by Focused Ultrasound-Mediated Blood-Brain Barrier Disruption: A Pilot Study |
title_full | Regulation of P-glycoprotein and Breast Cancer Resistance Protein Expression Induced by Focused Ultrasound-Mediated Blood-Brain Barrier Disruption: A Pilot Study |
title_fullStr | Regulation of P-glycoprotein and Breast Cancer Resistance Protein Expression Induced by Focused Ultrasound-Mediated Blood-Brain Barrier Disruption: A Pilot Study |
title_full_unstemmed | Regulation of P-glycoprotein and Breast Cancer Resistance Protein Expression Induced by Focused Ultrasound-Mediated Blood-Brain Barrier Disruption: A Pilot Study |
title_short | Regulation of P-glycoprotein and Breast Cancer Resistance Protein Expression Induced by Focused Ultrasound-Mediated Blood-Brain Barrier Disruption: A Pilot Study |
title_sort | regulation of p-glycoprotein and breast cancer resistance protein expression induced by focused ultrasound-mediated blood-brain barrier disruption: a pilot study |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9779754/ https://www.ncbi.nlm.nih.gov/pubmed/36555129 http://dx.doi.org/10.3390/ijms232415488 |
work_keys_str_mv | AT contiallegra regulationofpglycoproteinandbreastcancerresistanceproteinexpressioninducedbyfocusedultrasoundmediatedbloodbrainbarrierdisruptionapilotstudy AT geffroyfrancoise regulationofpglycoproteinandbreastcancerresistanceproteinexpressioninducedbyfocusedultrasoundmediatedbloodbrainbarrierdisruptionapilotstudy AT kamimurahermesas regulationofpglycoproteinandbreastcancerresistanceproteinexpressioninducedbyfocusedultrasoundmediatedbloodbrainbarrierdisruptionapilotstudy AT novellanthony regulationofpglycoproteinandbreastcancerresistanceproteinexpressioninducedbyfocusedultrasoundmediatedbloodbrainbarrierdisruptionapilotstudy AT tourniernicolas regulationofpglycoproteinandbreastcancerresistanceproteinexpressioninducedbyfocusedultrasoundmediatedbloodbrainbarrierdisruptionapilotstudy AT meriauxsebastien regulationofpglycoproteinandbreastcancerresistanceproteinexpressioninducedbyfocusedultrasoundmediatedbloodbrainbarrierdisruptionapilotstudy AT larratbenoit regulationofpglycoproteinandbreastcancerresistanceproteinexpressioninducedbyfocusedultrasoundmediatedbloodbrainbarrierdisruptionapilotstudy |