Age-dependent changes at the blood-brain barrier. A Comparative structural and functional study in young adult and middle aged rats

• Published in: Brain research bulletin Vol. 139; pp. 269 - 277
• Main Authors: Bors, Luca, Tóth, Kinga, Tóth, Estilla Zsófia, Bajza, Ágnes, Csorba, Attila, Szigeti, Krisztián, Máthé, Domokos, Perlaki, Gábor, Orsi, Gergely, Tóth, Gábor K., Erdő, Franciska
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.05.2018
• Subjects: Age Factors; Aging; Aging - physiology; Animals; Area Under Curve; ATP Binding Cassette Transporter, Subfamily B, Member 1 - metabolism; ATP Binding Cassette Transporter, Subfamily B, Member 1 - ultrastructure; Blood-brain barrier; Blood-Brain Barrier - diagnostic imaging; Blood-Brain Barrier - metabolism; Blood-Brain Barrier - physiology; Blood-Brain Barrier - ultrastructure; Chromatography, Liquid; Glial Fibrillary Acidic Protein - metabolism; Glial Fibrillary Acidic Protein - ultrastructure; Imaging; Magnetic Resonance Imaging; Male; Microdialysis; Microvessels - metabolism; Microvessels - ultrastructure; P-Glycoprotein; Rats; Rats, Wistar; Tandem Mass Spectrometry; Tight Junctions - metabolism; Tight Junctions - ultrastructure; Tomography, Emission-Computed, Single-Photon; ABC; BBB; DMSO; MRI; MIBI; LV; PRM; SPECT; AUC; STR; DV; Blood-brain barrier; Imaging; NHS; Aging; MDR; P-Glycoprotein; HPLC; ML; Cmax; P-gp; TR/TE; aPPF; FOV; IV; AP; GFAP; HESI; PB; Microdialysis; RF; LCMS–MS; TJ; aCSF; NGS
• ISSN: 0361-9230; 1873-2747; 1873-2747
• DOI: 10.1016/j.brainresbull.2018.03.001

[Display omitted] •There are structural changes at the blood-brain barrier (BBB) with aging.•Microdialysis and SPECT data suggest reduced function of P-pg at the BBB with aging.•Immunohistochemistry revealed a reduced expression of P-gp in the brain with aging.•The brain exposure to quinidine after P-gp inhibition increased more in young rats. Decreased beta-amyloid clearance in Alzheimer’s disease and increased blood-brain barrier permeability in aged subjects have been reported in several articles. However, morphological and functional characterization of blood-brain barrier and its membrane transporter activity have not been described in physiological aging yet. The aim of our study was to explore the structural changes in the brain microvessels and possible functional alterations of P-glycoprotein at the blood-brain barrier with aging. Our approach included MR imaging for anatomical orientation in middle aged rats, electronmicroscopy and immunohistochemistry to analyse the alterations at cellular level, dual or triple-probe microdialysis and SPECT to test P-glycoprotein functionality in young and middle aged rats. Our results indicate that the thickness of basal lamina increases, the number of tight junctions decreases and the size of astrocyte endfeet extends with advanced age. On the basis of microdialysis and SPECT results the P-gp function is reduced in old rats. With our multiparametric approach a complex regulation can be suggested which includes elements leading to increased permeability of blood-brain barrier by enhanced paracellular and transcellular transport, and factors working against it. To verify the role of P-gp pumps in brain aging further studies are warranted.