Brain clearance
Perivascular spaces are unique to the brain and contribute to waste clearance and fluid homeostasis. Impaired clearance may lead to accumulation of toxic proteins in various types of dementia, such as Alzheimer’s disease and cerebral amyloid angiopathy (CAA). We study the anatomy of the perivascular system, its driving forces (e.g. cardiac contraction, respiration, vasomotion) and how sleep, aging, and cardiovascular pathologies such as hypertension and blood-brain barrier dysfunction affect brain clearance.
The role of sleep in brain clearance
Investigator: Nina Smets
Support: NWO
In this project we study the anatomy of perivascular spaces, the driving forces for perivascular flow, and how these parameters are affected by sleep and hypertension. We use 2-photon imaging and immunohistochemistry to address our research questions.
Team: Erik N.T.P. Bakker, Gustav J. Strijkers, Bram F. Coolen, (Thijs) M.J.P. van Osch (LUMC), Lydiane Hirschler (LUMC), Balázs ÖRZSIK (LUMC), Judith de Vos.
The impact of blood-brain barrier dysfunction on brain clearance
Investigator: Shakira van der Panne
Support: Zon MW, Alzheimer Nederland
In this project we study the impact of blood-brain barrier (BBB) dysfunction on brain clearance via perivascular spaces. BBB dysfunction is a common denominator of several cerebrovascular and neurodegenerative diseases. Breakdown of the BBB leads to leakage of blood proteins into the perivascular space. We will use MRI, ultrasound, immunohistochemistry and confocal imaging to study how BBB disruption affects physiological waste clearance and fluid homeostasis.
Team: Gustav J. Strijkers, Elga H.E. de Vries, Louise van der Weerd (LUMC), Erik N.T.P. Bakker.
Taken from: T. Georgakopoulou, AE van der Wijk, E. van Bavel and E.N.T.P. Bakker. Microvasc Res 2023
A Translational Approach Towards Understanding Brain Waste Clearance in Cerebral Amyloid Angiopathy
Investigator: Ellen Vermeersch
Support: Leducq Foundation
Many neurodegenerative diseases are thought to be caused or accelerated by impaired brain clearance. One of these diseases is cerebral amyloid angiopathy (CAA) in which a toxic protein, called amyloid-β, accumulates in the vessel wall, leading to hemorrhagic stroke and dementia. We aim to elucidate fundamental unanswered questions related to brain clearance by focusing on both healthy brains and brains affected by CAA. This is done in a translational (from rodent to man), multimodal (from electron and multi-photon microscopy to MRI), and multidisciplinary (from mechanistic modeling to clinical) fashion.
Team: Matthias J.P. van Osch, Erik N.T.P. Bakker. Consortium members: Susanne J. van Veluw, Helene Benveniste, Jeffrey J. Iliff, Andy Y. Shih, Roxana O. Carare, Sylvie Lorthois, William E. Van Nostrand, Gabor C. Petzold, Steven M. Greenberg.
Beating brain dysfunction: elucidating the role of arterial pulsations in glymphatic clearance and cognitive impairment
Investigator: Daphne Naessens
Support: Dutch Heart Foundation, DCVA Heart-Brain Connection crossroads (HBCx)
Hypertension has emerged as an important risk factor for cognitive impairment and dementia, including Alzheimer’s disease. We obtained cerebrospinal fluid from spontaneously hypertensive rats (SHR) that were either left untreated or treated with two different antihypertensive medications from a relatively young age onwards. One group of SHR was treated with amlodipine, a calcium channel blocker, while another group received atenolol, a β-blocker. In this project we study the impact of antihypertensive treatment on CSF composition, to determine which type of medication is most beneficial for the brain. We will use proteomics and immunohistochemistry in this project.
Team: Nina G. Smets, Erik N.T.P. Bakker.
The role of sleep in brain clearance and prevention of Alzheimer’s disease
Investigator: Daphne Naessens
Support: Alzheimer Nederland
Sleep is essential for normal brain function, but it remains unclear through which mechanisms this occurs. Animal studies suggested that sleep facilitates clearance of waste products from the brain, and that this becomes less efficient with aging and several pathological conditions. Subsequent work in both humans and animals showed that sleep improves removal of the Alzheimer’s disease protein, amyloid-β, and that sleep deprivation increased parenchymal amyloid-β burden. Although the role of sleep in brain clearance seems evident, the exact mechanisms are still not fully understood. In this project, we will investigate whether sleep enhances clearance of waste products. We will use MRI in this project on awake and sleeping/sedated animals.
Team: Erik N.T.P. Bakker, Gustav J. Strijkers, Bram F. Coolen.
Lasering Psoriasis away
Investigator: Meagan Doppegieter
Support: Health Holland, TKI-PPP grant
In this project we test the hypothesis that pulsed dye laser treatment reduces the symptoms of psoriasis by destruction of the perivascular nerve endings via heating of the blood vessels. By gaining insight in the mechanism of action of laser treatment, we aim to develop a model to predict laser settings for individualized optimal treatment.
Team: Ton A.G.J.M. van Leeuwen, Maurice C.G. Aalders, Leah S. Wilk, Nick van der Beek, Erik N.T.P. Bakker
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Perivascular spaces around arteries exceed perivenous spaces in the mouse brain
Smets, N. G., van der Panne, S. A., Strijkers, G. J. & Bakker, E. N. T. P., Dec 2024, In: Scientific reports. 14, 1, 17655.Research output: Contribution to journal › Article › Academic › peer-review
The impact of temperature on vascular function in connection with vascular laser treatment
Doppegieter, M., van Leeuwen, T. G., Aalders, M. C. G., de Vos, J., van Bavel, E. T. & Bakker, E. N. T. P., 1 Dec 2024, In: Lasers in medical science. 39, 1, 122.Research output: Contribution to journal › Article › Academic › peer-review
Is CAA a perivascular brain clearance disease? A discussion of the evidence to date and outlook for future studies
van Veluw, S. J., Benveniste, H., Bakker, E. N. T. P., Carare, R. O., Greenberg, S. M., Iliff, J. J., Lorthois, S., Van Nostrand, W. E., Petzold, G. C., Shih, A. Y. & van Osch, M. J. P., Dec 2024, In: Cellular and molecular life sciences. 81, 1, 239.Research output: Contribution to journal › Review article › Academic › peer-review
Medin, a link between vascular pathology and dementia?
Altenburg, I. S., Smets, N. G., Strijkers, G. J. & Bakker, E. N. T., Dec 2024, In: Journal of cerebral blood flow and metabolism. 44, 12, p. 1403-1408 6 p.Research output: Contribution to journal › Review article › Academic › peer-review
Cerebrospinal fluid turnover as a driver of brain clearance
Smets, N. G., Strijkers, G. J., Vinje, V. & Bakker, E. N. T. P., Jul 2024, In: NMR in biomedicine.Research output: Contribution to journal › Article › Academic › peer-review
A translational approach towards understanding brain waste clearance in cerebral amyloid angiopathy
Leducq Foundation Transatlantic Network of Excellence on Brain Clearance & Bakker, E. N. T. P., 7 May 2024, In: European heart journal. 45, 17, p. 1500-1502 3 p.Research output: Contribution to journal › Article › Academic › peer-review
Current Understanding of the Anatomy, Physiology, and Magnetic Resonance Imaging of Neurofluids: Update From the 2022 “ISMRM Imaging Neurofluids Study group” Workshop in Rome
Agarwal, N., Lewis, L. D., Hirschler, L., Rivera, L. R., Naganawa, S., Levendovszky, S. R., Ringstad, G., Klarica, M., Wardlaw, J., Iadecola, C., Hawkes, C., Carare, R. O., Wells, J., Bakker, E. N. T. P., Kurtcuoglu, V., Bilston, L., Nedergaard, M., Mori, Y., Stoodley, M. & Alperin, N. & 2 others, , Feb 2024, In: Journal of magnetic resonance imaging. 59, 2, p. 431-449 19 p.Research output: Contribution to journal › Review article › Academic › peer-review
Subminute thermal damage to cell types present in the skin
Doppegieter, M., van Leeuwen, T. G., van Weert, A., Aalders, M. C. G. & Bakker, E. T. P., 2024, In: International journal of hyperthermia. 41, 1, 2354435.Research output: Contribution to journal › Article › Academic › peer-review
Effect of long-term antihypertensive treatment on cerebrovascular structure and function in hypertensive rats
Naessens, D. M. P., de Vos, J., Richard, E., Wilhelmus, M. M. M., Jongenelen, C. A. M., Scholl, E. R., van der Wel, N. N., Heijst, J. A., Teunissen, C. E., Strijkers, G. J., Coolen, B. F., VanBavel, E. & Bakker, E. N. T. P., 1 Dec 2023, In: Scientific reports. 13, 1, 3481.Research output: Contribution to journal › Article › Academic › peer-review
Extravasation of biodegradable microspheres in the rat brain
van der Wijk, A.-E., Georgakopoulou, T., Steendam, R., Zuidema, J., Hordijk, P. L., Bakker, E. N. T. P. & van Bavel, E., 1 Dec 2023, In: Drug delivery. 30, 1, p. 2194579 1 p., 2194579.Research output: Contribution to journal › Article › Academic › peer-review
Effects of pulsed dye laser treatment in psoriasis: A nerve-wrecking process?
Doppegieter, M., van der Beek, N., Bakker, E. N. T. P., Neumann, M. H. A. & van Bavel, E., Jul 2023, In: Experimental dermatology. 32, 7, p. 1165-1173 9 p.Research output: Contribution to journal › Article › Academic › peer-review
Perivascular clearance of blood proteins after blood-brain barrier disruption in a rat model of microinfarcts
Georgakopoulou, T., van der Wijk, A.-E., van Bavel, E. & Bakker, E. N. T. P., 1 Jul 2023, In: Microvascular research. 148, 104515.Research output: Contribution to journal › Article › Academic › peer-review
Mechanistic and therapeutic role of NLRP3 inflammasome in the pathogenesis of Alzheimer's disease
Jha, D., Bakker, E. N. T. P. & Kumar, R., 2023, (E-pub ahead of print) In: Journal of neurochemistry.Research output: Contribution to journal › Review article › Academic › peer-review
Physiology of Glymphatic Solute Transport and Waste Clearance from the Brain
Zhao, L., Tannenbaum, A., Bakker, E. N. T. P. & Benveniste, H., 1 Nov 2022, In: Physiology (Bethesda, Md.). 37, 6, p. 0 1 p.Research output: Contribution to journal › Review article › Academic › peer-review
Brain solute transport is more rapid in periarterial than perivenous spaces
Vinje, V., Bakker, E. N. T. P. & Rognes, M. E., 1 Dec 2021, In: Scientific reports. 11, 1, 16085.Research output: Contribution to journal › Article › Academic › peer-review
Quantitative 3D analysis of tissue damage in a rat model of microembolization
Georgakopoulou, T., van der Wijk, A.-E., Bakker, E. N. T. P., vanBavel, E., Majoie, C., Marquering, H., van Bavel, E., Hoekstra, A., Dippel, D., Lingsma, H., van der Lugt, A., Samuels, N., Boodt, N., Roos, Y., de Meyer, S., Staessens, S., Vandelanotte, S., Konduri, P., Terreros, N. A. & Chopard, B. & 25 others, , 9 Nov 2021, In: Journal of biomechanics. 128, 110723.Research output: Contribution to journal › Article › Academic › peer-review
Erratum to 'Recovery of Hypoxic Regions in a Rat Model of Microembolism' [Journal of Stroke and Cerebrovascular Diseases, Vol. 30, No. 6 (June), 2021: 105739]
INSIST investigators, Nov 2021, In: Journal of stroke and cerebrovascular diseases. 30, 11, 105967.Research output: Contribution to journal › Comment/Letter to the editor › Academic
Recovery of Hypoxic Regions in a Rat Model of Microembolism
Georgakopoulou, T., van der Wijk, A.-E., Bakker, E. N. T. P. & vanBavel, E., 1 Jun 2021, In: Journal of stroke and cerebrovascular diseases. 30, 6, 105739.Research output: Contribution to journal › Article › Academic › peer-review
Mapping Solute Clearance From the Mouse Hippocampus Using a 3D Imaging Cryomicrotome
Naessens, D. M. P., Dobbe, J. G. G., de Vos, J., VanBavel, E. & Bakker, E. N. T. P., 22 Mar 2021, In: Frontiers in neuroscience. 15, 631325.Research output: Contribution to journal › Article › Academic › peer-review
Biomechanics in Small Artery Remodeling
Bakker, E. N. T. P. & van Bavel, E., 2021, Cardiac and Vascular Biology. Springer Science and Business Media Deutschland GmbH, Vol. 8. p. 47-68 22 p. (Cardiac and Vascular Biology; vol. 8).Research output: Chapter in Book/Report/Conference proceeding › Chapter › Academic › peer-review
We have internships available for bachelor and master students who are interested in the vascular contribution to dementia. We perform preclinical studies, focused on brain clearance via perivascular spaces (glymphatics). We study how disruption of the blood-brain barrier, hypertension, and sleep affect driving forces and waste clearance from the brain. Techniques involve MRI, intravital microscopy, immunohistochemistry, electron microscopy, and ex-vivo vascular functional analyses.
For more information, contact Erik Bakker at n.t.bakker@amsterdamumc.nl