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Fusogenic Liposomes Deliver Resveratrol to Brain Microcirculation and Improve Neurovascular Coupling in Aged Mice

Adjustment of cerebral blood flow (CBF) to the increased oxygen and nutrient demands of active brain regions via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In advanced age, cerebromicrovascular oxidative stress and endothelial dysfunction impair...

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Autores principales: Toth, Adam Nyul, Wiedenhoeft, Tabea, Tarantini, Stefano, Csipo, Tamas, Balasubramanian, Priya, Csiszar, Anna, Csiszar, Agnes, Ungvari, Zoltan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7741245/
http://dx.doi.org/10.1093/geroni/igaa057.394
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author Toth, Adam Nyul
Wiedenhoeft, Tabea
Tarantini, Stefano
Csipo, Tamas
Balasubramanian, Priya
Csiszar, Anna
Csiszar, Agnes
Ungvari, Zoltan
author_facet Toth, Adam Nyul
Wiedenhoeft, Tabea
Tarantini, Stefano
Csipo, Tamas
Balasubramanian, Priya
Csiszar, Anna
Csiszar, Agnes
Ungvari, Zoltan
author_sort Toth, Adam Nyul
collection PubMed
description Adjustment of cerebral blood flow (CBF) to the increased oxygen and nutrient demands of active brain regions via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In advanced age, cerebromicrovascular oxidative stress and endothelial dysfunction impair neurovascular coupling, contributing to age-related cognitive decline. Recently we developed a resveratrol (3,4′,5- trihydroxystilbene)-containing fusogenic liposome (FL-RSV)-based molecular delivery system that can effectively target cultured cerebromicrovascular endothelial cells, attenuating age-related oxidative stress. To assess the cerebromicrovascular protective effects of FL-RSV in vivo, aged (24-monthold) C57BL/6 mice were treated with FL-RSV for four days. To demonstrate effective cellular uptake of FL-RSV, accumulation of the lipophilic tracer dyes in cells of the neurovascular unit was confirmed using two-photon imaging (through a chronic cranial window). NVC was assessed by measuring CBF responses (laser speckle contrast imaging) evoked by contralateral whisker stimulation. We found that NVC responses were significantly impaired in aged mice. Treatment with FL-RSV significantly improved NVC responses by increasing NO-mediated vasodilation. These findings are paralleled by the protective effects of FL-RSV on endothelium-dependent relaxation in the aorta. Thus, treatment with FL-RSV rescues endothelial function and NVC responses in aged mice. We propose that resveratrol containing fusogenic liposomes could also be used for combined delivery of various anti-geronic factors, including proteins, small molecules, DNA vectors and mRNAs targeting key pathways involved in microvascular aging and neurovascular dysfunction for the prevention/treatment of age-related cerebromicrovascular pathologies and development of vascular cognitive impairment (VCI) in aging.
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spelling pubmed-77412452020-12-21 Fusogenic Liposomes Deliver Resveratrol to Brain Microcirculation and Improve Neurovascular Coupling in Aged Mice Toth, Adam Nyul Wiedenhoeft, Tabea Tarantini, Stefano Csipo, Tamas Balasubramanian, Priya Csiszar, Anna Csiszar, Agnes Ungvari, Zoltan Innov Aging Abstracts Adjustment of cerebral blood flow (CBF) to the increased oxygen and nutrient demands of active brain regions via neurovascular coupling (NVC) has an essential role in maintenance of healthy cognitive function. In advanced age, cerebromicrovascular oxidative stress and endothelial dysfunction impair neurovascular coupling, contributing to age-related cognitive decline. Recently we developed a resveratrol (3,4′,5- trihydroxystilbene)-containing fusogenic liposome (FL-RSV)-based molecular delivery system that can effectively target cultured cerebromicrovascular endothelial cells, attenuating age-related oxidative stress. To assess the cerebromicrovascular protective effects of FL-RSV in vivo, aged (24-monthold) C57BL/6 mice were treated with FL-RSV for four days. To demonstrate effective cellular uptake of FL-RSV, accumulation of the lipophilic tracer dyes in cells of the neurovascular unit was confirmed using two-photon imaging (through a chronic cranial window). NVC was assessed by measuring CBF responses (laser speckle contrast imaging) evoked by contralateral whisker stimulation. We found that NVC responses were significantly impaired in aged mice. Treatment with FL-RSV significantly improved NVC responses by increasing NO-mediated vasodilation. These findings are paralleled by the protective effects of FL-RSV on endothelium-dependent relaxation in the aorta. Thus, treatment with FL-RSV rescues endothelial function and NVC responses in aged mice. We propose that resveratrol containing fusogenic liposomes could also be used for combined delivery of various anti-geronic factors, including proteins, small molecules, DNA vectors and mRNAs targeting key pathways involved in microvascular aging and neurovascular dysfunction for the prevention/treatment of age-related cerebromicrovascular pathologies and development of vascular cognitive impairment (VCI) in aging. Oxford University Press 2020-12-16 /pmc/articles/PMC7741245/ http://dx.doi.org/10.1093/geroni/igaa057.394 Text en © The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Abstracts
Toth, Adam Nyul
Wiedenhoeft, Tabea
Tarantini, Stefano
Csipo, Tamas
Balasubramanian, Priya
Csiszar, Anna
Csiszar, Agnes
Ungvari, Zoltan
Fusogenic Liposomes Deliver Resveratrol to Brain Microcirculation and Improve Neurovascular Coupling in Aged Mice
title Fusogenic Liposomes Deliver Resveratrol to Brain Microcirculation and Improve Neurovascular Coupling in Aged Mice
title_full Fusogenic Liposomes Deliver Resveratrol to Brain Microcirculation and Improve Neurovascular Coupling in Aged Mice
title_fullStr Fusogenic Liposomes Deliver Resveratrol to Brain Microcirculation and Improve Neurovascular Coupling in Aged Mice
title_full_unstemmed Fusogenic Liposomes Deliver Resveratrol to Brain Microcirculation and Improve Neurovascular Coupling in Aged Mice
title_short Fusogenic Liposomes Deliver Resveratrol to Brain Microcirculation and Improve Neurovascular Coupling in Aged Mice
title_sort fusogenic liposomes deliver resveratrol to brain microcirculation and improve neurovascular coupling in aged mice
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7741245/
http://dx.doi.org/10.1093/geroni/igaa057.394
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