Focal solute trapping and global glymphatic pathway impairment in a murine model of multiple microinfarcts

Minghuan Wang, Fengfei Ding, Sai Yue Deng, Xuequn Guo, Wei Wang, Jeffrey Iliff, Maiken Nedergaard

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

Microinfarcts occur commonly in the aging brain as a consequence of diffuse embolic events and are associated with the development of vascular dementia and Alzheimer’s disease. However, the manner in which disperse microscopic lesions reduce global cognitive function and increase the risk for Alzheimer’s disease is unclear. The glymphatic system, which is a brain-wide perivascular network that supports the recirculation of CSF through the brain parenchyma, facilitates the clearance of interstitial solutes including amyloid _ and tau. We investigated whether glymphatic pathway function is impaired in a murine model of multiple microinfarcts induced by intraarterial injection of cholesterol crystals. The analysis showed that multiple microinfarcts markedly impaired global influx of CSF along the glymphatic pathway. Although suppression of global glymphatic function was transient, resolving within 2 weeks of injury, CSF tracers also accumulated within tissue associated with microinfarcts. The effect of diffuse microinfarcts on global glymphatic pathway function was exacerbated in the mice aged 12 months compared with the 2-to 3-month-old mice. These findings indicate that glymphatic function is focally disrupted around microinfarcts and that the aging brain is more vulnerable to this disruption than the young brain. These observations suggest that microlesions may trap proteins and other interstitial solutes within the brain parenchyma, increasing the risk of amyloid plaque formation.

Original languageEnglish (US)
Pages (from-to)2870-2877
Number of pages8
JournalJournal of Neuroscience
Volume37
Issue number11
DOIs
StatePublished - Mar 15 2017

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Brain
Alzheimer Disease
Intra-Arterial Injections
Vascular Dementia
Amyloid Plaques
Vascular Diseases
Amyloid
Cognition
Cholesterol
Wounds and Injuries
Proteins

Keywords

  • Glymphatic
  • Microinfarct
  • Vascular dementia

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Focal solute trapping and global glymphatic pathway impairment in a murine model of multiple microinfarcts. / Wang, Minghuan; Ding, Fengfei; Deng, Sai Yue; Guo, Xuequn; Wang, Wei; Iliff, Jeffrey; Nedergaard, Maiken.

In: Journal of Neuroscience, Vol. 37, No. 11, 15.03.2017, p. 2870-2877.

Research output: Contribution to journalArticle

Wang, Minghuan ; Ding, Fengfei ; Deng, Sai Yue ; Guo, Xuequn ; Wang, Wei ; Iliff, Jeffrey ; Nedergaard, Maiken. / Focal solute trapping and global glymphatic pathway impairment in a murine model of multiple microinfarcts. In: Journal of Neuroscience. 2017 ; Vol. 37, No. 11. pp. 2870-2877.
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