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Brain Res Bull. 2018 May;139:269-277. doi: 10.1016/j.brainresbull.2018.03.001. Epub 2018 Mar 6.

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

Author information

1
Pázmány Péter Catholic University, Faculty of Information Technology and Bionics, Práter u. 50a, H-1083 Budapest.
2
Hungarian Academy of Sciences, Institute of Cognitive Neuroscience and Psychology, Magyar tudósok körútja 2. H-1117 Budapest.
3
University of Szeged, Faculty of Pharmacy, Deparment of Pharmacognosy, Eötvös u. 6, H-6720 Szeged.
4
Semmelweis University, Faculty of Medicine, Department of Biophysics and Radiation Biology, Tűzoltó u. 37-47, H-1094 Budapest.
5
Semmelweis University, Faculty of Medicine, Department of Biophysics and Radiation Biology, Tűzoltó u. 37-47, H-1094 Budapest,; CROmed Translational Research Ltd. Budapest.
6
MTA-PTE Clinical Neuroscience MR Research Group, Ret u. 2, H-7623 Pecs, Hungary; Department of Neurosurgery, University of Pecs, Medical School, Ret u. 2, H-7623 Pecs, Hungary.
7
Department of Medical Chemistry, Faculty of Medicine, University of Szeged, Dóm tér 8, H-6720, Szeged, Hungary.
8
Pázmány Péter Catholic University, Faculty of Information Technology and Bionics, Práter u. 50a, H-1083 Budapest. Electronic address: erdo.franciska@itk.ppke.hu.

Abstract

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.

KEYWORDS:

Aging; Blood-brain barrier; Imaging; Microdialysis; P-Glycoprotein

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