Enhanced interstitial fluid drainage in the hippocampus of spontaneously hypertensive rats

Abstract Hypertension is associated with cognitive decline and various forms of dementia, including Alzheimer’s disease. In animal models of hypertension, many of Alzheimer’s disease characteristics are recapitulated, including brain atrophy, cognitive decline, amyloid β accumulation and blood brain...

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Autores principales:	Beatrice Bedussi, Daphne M. P. Naessens, Judith de Vos, Rik Olde Engberink, Micha M. M. Wilhelmus, Edo Richard, Malyssa ten Hove, Ed vanBavel, Erik N. T. P. Bakker
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/38c8fa3d5f69496cb0971bd9b1f35342
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spelling	oai:doaj.org-article:38c8fa3d5f69496cb0971bd9b1f353422021-12-02T12:32:44ZEnhanced interstitial fluid drainage in the hippocampus of spontaneously hypertensive rats10.1038/s41598-017-00861-x2045-2322https://doaj.org/article/38c8fa3d5f69496cb0971bd9b1f353422017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00861-xhttps://doaj.org/toc/2045-2322Abstract Hypertension is associated with cognitive decline and various forms of dementia, including Alzheimer’s disease. In animal models of hypertension, many of Alzheimer’s disease characteristics are recapitulated, including brain atrophy, cognitive decline, amyloid β accumulation and blood brain barrier dysfunction. Removal of amyloid β and other waste products depends in part on clearance via the brain interstitial fluid (ISF). Here we studied the impact of hypertension on ISF drainage, using spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). At 8 months, high (500 kD) and low (3 kD) fluorescent molecular weight tracers released passively into the hippocampus showed a drastically enhanced spreading in SHR. Tracer spreading was inhomogeneous, with accumulation at ISF-CSF borders, around arteries, and towards the stratum lacunosum moleculare. These locations stained positively for the astrocyte marker GFAP, and aquaporin 4. Despite enhanced dispersion, clearance of tracers was not affected in SHR. In conclusion, these data indicate enhanced bulk flow of ISF in the hippocampus of hypertensive rats. ISF drains along astrocytes towards the cerebrospinal fluid compartment, which leads to sieving of high molecular weight solutes. Sieving may lead to a local increase in the concentration of waste products and potentially promotes the aggregation of amyloid β.Beatrice BedussiDaphne M. P. NaessensJudith de VosRik Olde EngberinkMicha M. M. WilhelmusEdo RichardMalyssa ten HoveEd vanBavelErik N. T. P. BakkerNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Beatrice Bedussi Daphne M. P. Naessens Judith de Vos Rik Olde Engberink Micha M. M. Wilhelmus Edo Richard Malyssa ten Hove Ed vanBavel Erik N. T. P. Bakker Enhanced interstitial fluid drainage in the hippocampus of spontaneously hypertensive rats
description	Abstract Hypertension is associated with cognitive decline and various forms of dementia, including Alzheimer’s disease. In animal models of hypertension, many of Alzheimer’s disease characteristics are recapitulated, including brain atrophy, cognitive decline, amyloid β accumulation and blood brain barrier dysfunction. Removal of amyloid β and other waste products depends in part on clearance via the brain interstitial fluid (ISF). Here we studied the impact of hypertension on ISF drainage, using spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY). At 8 months, high (500 kD) and low (3 kD) fluorescent molecular weight tracers released passively into the hippocampus showed a drastically enhanced spreading in SHR. Tracer spreading was inhomogeneous, with accumulation at ISF-CSF borders, around arteries, and towards the stratum lacunosum moleculare. These locations stained positively for the astrocyte marker GFAP, and aquaporin 4. Despite enhanced dispersion, clearance of tracers was not affected in SHR. In conclusion, these data indicate enhanced bulk flow of ISF in the hippocampus of hypertensive rats. ISF drains along astrocytes towards the cerebrospinal fluid compartment, which leads to sieving of high molecular weight solutes. Sieving may lead to a local increase in the concentration of waste products and potentially promotes the aggregation of amyloid β.
format	article
author	Beatrice Bedussi Daphne M. P. Naessens Judith de Vos Rik Olde Engberink Micha M. M. Wilhelmus Edo Richard Malyssa ten Hove Ed vanBavel Erik N. T. P. Bakker
author_facet	Beatrice Bedussi Daphne M. P. Naessens Judith de Vos Rik Olde Engberink Micha M. M. Wilhelmus Edo Richard Malyssa ten Hove Ed vanBavel Erik N. T. P. Bakker
author_sort	Beatrice Bedussi
title	Enhanced interstitial fluid drainage in the hippocampus of spontaneously hypertensive rats
title_short	Enhanced interstitial fluid drainage in the hippocampus of spontaneously hypertensive rats
title_full	Enhanced interstitial fluid drainage in the hippocampus of spontaneously hypertensive rats
title_fullStr	Enhanced interstitial fluid drainage in the hippocampus of spontaneously hypertensive rats
title_full_unstemmed	Enhanced interstitial fluid drainage in the hippocampus of spontaneously hypertensive rats
title_sort	enhanced interstitial fluid drainage in the hippocampus of spontaneously hypertensive rats
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/38c8fa3d5f69496cb0971bd9b1f35342
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Enhanced interstitial fluid drainage in the hippocampus of spontaneously hypertensive rats

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