TY - JOUR
T1 - Enhanced interstitial fluid drainage in the hippocampus of spontaneously hypertensive rats
AU - Bedussi, Beatrice
AU - Naessens, Daphne M.P.
AU - de Vos, Judith
AU - Olde Engberink, Rik
AU - Wilhelmus, Micha M.M.
AU - Richard, Edo
AU - Ten Hove, Malyssa
AU - Vanbavel, Ed
AU - Bakker, Erik N.T.P.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85019008215&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41598-017-00861-x
DO - https://doi.org/10.1038/s41598-017-00861-x
M3 - Article
C2 - 28389645
SN - 2045-2322
VL - 7
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 744
ER -