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001-es BibID:BIBFORM099945
035-os BibID:(WOS)000492573700002 (Scopus)85074572605
Első szerző:Wiedenhoeft, Tabea
Cím:Fusogenic liposomes effectively deliver resveratrol to the cerebral microcirculation and improve endothelium-dependent neurovascular coupling responses in aged mice / Wiedenhoeft Tabea, Tarantini Stefano, Nyúl-Tóth Ádám, Yabluchanskiy Andriy, Csipo Tamas, Balasubramanian Priya, Lipecz Agnes, Kiss Tamas, Csiszar Anna, Csiszar Agnes, Ungvari Zoltan
Dátum:2019
ISSN:2509-2715 2509-2723
Megjegyzések: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-month-old) 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.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
folyóiratcikk
Aging
Cerebral circulation
Endothelial dysfunction
Endothelium
Functional hyperemia
Fusogenic liposomes
Oxidative stress
Resveratrol
Vascular cognitive impairment
Megjelenés:GeroScience. - 41 : 6 (2019), p. 711-725. -
További szerzők:Tarantini, Stefano Nyúl-Tóth Ádám Yabluchanskiy, Andriy Csípő Tamás (1990-) Balasubramanian, Priya Lipécz Ágnes Kiss Tamás (1950-) (vegyész) Csiszár Anna Csiszár Ágnes Ungvári Zoltán
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