Cerebrospinal fluid circulation and the glymphatic system in health and disease
Kritsilis, Marios LU
(2025)
In Lund University, Faculty of Medicine Doctoral Dissertation Series 2025:59
- Abstract
- Cerebrospinal fluid (CSF) circulation is a complex process that is still not fully understood. Despite decades of research on CSF and its distinct functions, there still remain a number of open questions regarding the mechanisms that govern its circulation. The recently discovered glymphatic system, which is mostly active during sleep, clears the brain from extracellular metabolites and waste products. Yet many parameters of these functions have not been investigated in several disease conditions, while the methods to study them are also constantly evolving.
This thesis aims to elucidate some of the mechanisms of CSF circulation and the glymphatic system in health and disease. The first study investigated how the glymphatic system... (More) - Cerebrospinal fluid (CSF) circulation is a complex process that is still not fully understood. Despite decades of research on CSF and its distinct functions, there still remain a number of open questions regarding the mechanisms that govern its circulation. The recently discovered glymphatic system, which is mostly active during sleep, clears the brain from extracellular metabolites and waste products. Yet many parameters of these functions have not been investigated in several disease conditions, while the methods to study them are also constantly evolving.
This thesis aims to elucidate some of the mechanisms of CSF circulation and the glymphatic system in health and disease. The first study investigated how the glymphatic system is affected by heart failure (HF). The study found evidence of dysregulation of brain fluid dynamics in mice with HF, while cerebral blood flow emerged as a potential new regulator of glymphatic clearance. The second study compared the efficacy of different lectins and staining methods in labeling cerebral vasculature as an important step for aquaporin-4 polarization studies, which is a crucial component of glymphatic function. The third study investigated the main pathways through which CSF leaves the central nervous system and confirmed that the nasal pathway is a major CSF efflux route that can readily adapt to different pathophysiological challenges. The fourth study looked at the interaction of amyloid beta (Aβ) in the CSF with glymphatic function using a pig model developed in our lab. The study found that CSF distribution and glymphatic influx were impaired in pigs injected with Aβ in the CSF, while Aβ was found to co-localize with elastin elements across the cerebral arterial walls.
Overall, these studies highlight the importance of understanding the mechanisms behind the glymphatic system and CSF circulation, and how they relate to various diseases.
(Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/3db3ca8e-2037-4023-a74b-a53a7d006e46
- author
- Kritsilis, Marios
LU
- supervisor
-
- Iben Lundgaard LU
- Anja Meissner LU
- opponent
-
- Professor Enger, Rune, University of Oslo, Norway
- organization
- publishing date
- 2025
- type
- Thesis
- publication status
- published
- subject
- keywords
- neurodegeneration, cardiovascular diseases, neurofluids, MRI, microscopy, animal models
- in
- Lund University, Faculty of Medicine Doctoral Dissertation Series 2025:59
- issue
- 2025:59
- pages
- 92 pages
- publisher
- Lund University, Faculty of Medicine
- defense location
- Belfragesalen, BMC D15, Klinikgatan 32 i Lund
- defense date
- 2025-05-07 13:15:00
- ISSN
- 1652-8220
- ISBN
- 978-91-8021-712-5
- language
- English
- LU publication?
- yes
- id
- 3db3ca8e-2037-4023-a74b-a53a7d006e46
- date added to LUP
- 2025-04-11 14:37:32
- date last changed
- 2025-04-17 09:57:24
@phdthesis{3db3ca8e-2037-4023-a74b-a53a7d006e46,
abstract = {{Cerebrospinal fluid (CSF) circulation is a complex process that is still not fully understood. Despite decades of research on CSF and its distinct functions, there still remain a number of open questions regarding the mechanisms that govern its circulation. The recently discovered glymphatic system, which is mostly active during sleep, clears the brain from extracellular metabolites and waste products. Yet many parameters of these functions have not been investigated in several disease conditions, while the methods to study them are also constantly evolving.<br/><br/>This thesis aims to elucidate some of the mechanisms of CSF circulation and the glymphatic system in health and disease. The first study investigated how the glymphatic system is affected by heart failure (HF). The study found evidence of dysregulation of brain fluid dynamics in mice with HF, while cerebral blood flow emerged as a potential new regulator of glymphatic clearance. The second study compared the efficacy of different lectins and staining methods in labeling cerebral vasculature as an important step for aquaporin-4 polarization studies, which is a crucial component of glymphatic function. The third study investigated the main pathways through which CSF leaves the central nervous system and confirmed that the nasal pathway is a major CSF efflux route that can readily adapt to different pathophysiological challenges. The fourth study looked at the interaction of amyloid beta (Aβ) in the CSF with glymphatic function using a pig model developed in our lab. The study found that CSF distribution and glymphatic influx were impaired in pigs injected with Aβ in the CSF, while Aβ was found to co-localize with elastin elements across the cerebral arterial walls.<br/><br/>Overall, these studies highlight the importance of understanding the mechanisms behind the glymphatic system and CSF circulation, and how they relate to various diseases.<br/>}},
author = {{Kritsilis, Marios}},
isbn = {{978-91-8021-712-5}},
issn = {{1652-8220}},
keywords = {{neurodegeneration; cardiovascular diseases; neurofluids; MRI; microscopy; animal models}},
language = {{eng}},
number = {{2025:59}},
publisher = {{Lund University, Faculty of Medicine}},
school = {{Lund University}},
series = {{Lund University, Faculty of Medicine Doctoral Dissertation Series 2025:59}},
title = {{Cerebrospinal fluid circulation and the glymphatic system in health and disease}},
url = {{https://lup.lub.lu.se/search/files/216938468/Marios_Kritsilis_-_WEBB.pdf}},
year = {{2025}},
}