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Loss of glymphatic homeostasis in heart failure

Kritsilis, Marios LU orcid ; Vanherle, Lotte LU ; Rosenholm, Marko ; In 't Zandt, René LU orcid ; Yao, Yuan ; Swanberg, Kelley M. LU orcid ; Weikop, Pia ; Gottschalk, Michael LU orcid ; Shanbhag, Nagesh LU and Luo, Jiebo , et al. (2025) In Brain 148(3). p.985-1000
Abstract
Heart failure (HF) is associated with progressive reduction in cerebral blood flow (CBF) and neurodegenerative changes leading to cognitive decline. The glymphatic system is crucial for the brain's waste removal, and its dysfunction is linked to neurodegeneration.

In this study, we used a mouse model of HF, induced by myocardial infarction (MI), to investigate the effects of HF with reduced ejection fraction on the brain’s glymphatic function.

Using dynamic contrast-enhanced MRI and high-resolution fluorescence microscopy, we found increased solute influx from the CSF spaces to the brain, i.e. glymphatic influx, at 12 weeks post MI. Two-photon microscopy revealed that cerebral arterial pulsatility, a major driver of the... (More)
Heart failure (HF) is associated with progressive reduction in cerebral blood flow (CBF) and neurodegenerative changes leading to cognitive decline. The glymphatic system is crucial for the brain's waste removal, and its dysfunction is linked to neurodegeneration.

In this study, we used a mouse model of HF, induced by myocardial infarction (MI), to investigate the effects of HF with reduced ejection fraction on the brain’s glymphatic function.

Using dynamic contrast-enhanced MRI and high-resolution fluorescence microscopy, we found increased solute influx from the CSF spaces to the brain, i.e. glymphatic influx, at 12 weeks post MI. Two-photon microscopy revealed that cerebral arterial pulsatility, a major driver of the glymphatic system, was potentiated at this timepoint, and could explain this increase in glymphatic influx. However, clearance of proteins from the brain parenchyma did not increase proportionately with influx, while a relative increase in brain parenchyma volume was found at 12 weeks post MI, suggesting dysregulation of brain fluid dynamics. Additionally, our results showed a correlation between brain clearance and CBF.

These findings highlight the role of CBF as a key regulator of the glymphatic system, suggesting its involvement in the development of brain disorders associated with reduced CBF. This study paves the way for future investigations into the effects of cardiovascular diseases on the brain's clearance mechanisms, which may provide novel insights into the prevention and treatment of cognitive decline. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Brain
volume
148
issue
3
pages
985 - 1000
publisher
Oxford University Press
external identifiers
  • pmid:39693238
  • scopus:86000736147
ISSN
1460-2156
DOI
10.1093/brain/awae411
language
English
LU publication?
yes
id
0ef54ec0-a9a7-4d60-b15c-9cbfb7806717
date added to LUP
2025-01-14 18:53:36
date last changed
2025-06-27 07:15:55
@article{0ef54ec0-a9a7-4d60-b15c-9cbfb7806717,
  abstract     = {{Heart failure (HF) is associated with progressive reduction in cerebral blood flow (CBF) and neurodegenerative changes leading to cognitive decline. The glymphatic system is crucial for the brain's waste removal, and its dysfunction is linked to neurodegeneration.<br/><br/>In this study, we used a mouse model of HF, induced by myocardial infarction (MI), to investigate the effects of HF with reduced ejection fraction on the brain’s glymphatic function.<br/><br/>Using dynamic contrast-enhanced MRI and high-resolution fluorescence microscopy, we found increased solute influx from the CSF spaces to the brain, i.e. glymphatic influx, at 12 weeks post MI. Two-photon microscopy revealed that cerebral arterial pulsatility, a major driver of the glymphatic system, was potentiated at this timepoint, and could explain this increase in glymphatic influx. However, clearance of proteins from the brain parenchyma did not increase proportionately with influx, while a relative increase in brain parenchyma volume was found at 12 weeks post MI, suggesting dysregulation of brain fluid dynamics. Additionally, our results showed a correlation between brain clearance and CBF.<br/><br/>These findings highlight the role of CBF as a key regulator of the glymphatic system, suggesting its involvement in the development of brain disorders associated with reduced CBF. This study paves the way for future investigations into the effects of cardiovascular diseases on the brain's clearance mechanisms, which may provide novel insights into the prevention and treatment of cognitive decline.}},
  author       = {{Kritsilis, Marios and Vanherle, Lotte and Rosenholm, Marko and In 't Zandt, René and Yao, Yuan and Swanberg, Kelley M. and Weikop, Pia and Gottschalk, Michael and Shanbhag, Nagesh and Luo, Jiebo and Boster, Kimberly and Nedergaard, Maiken and Meissner, Anja and Lundgaard, Iben}},
  issn         = {{1460-2156}},
  language     = {{eng}},
  number       = {{3}},
  pages        = {{985--1000}},
  publisher    = {{Oxford University Press}},
  series       = {{Brain}},
  title        = {{Loss of glymphatic homeostasis in heart failure}},
  url          = {{http://dx.doi.org/10.1093/brain/awae411}},
  doi          = {{10.1093/brain/awae411}},
  volume       = {{148}},
  year         = {{2025}},
}