Sizes and shapes of perivascular spaces surrounding murine pial arteries

Fluids and Barriers of the CNS

Research

Maiken Nedergaard¹  Antonio Ladrón-de-Guevara²  Ting Du³  Douglas H. Kelley⁴  Nikola Raicevic⁴  Kimberly Boster⁴  Jarod M. Forer⁴ 

[1] Center for Translational Neuromedicine and Department of Neuroscience, University of Rochester Medical Center, Rochester, USA;Center for Translational Neuromedicine and Department of Neuroscience, University of Rochester Medical Center, Rochester, USA;Department of Biomedical Engineering, University of Rochester, Rochester, USA;Center for Translational Neuromedicine and Department of Neuroscience, University of Rochester Medical Center, Rochester, USA;School of Pharmacy, China Medical University, Shenyang, Liaoning, China;Department of Mechanical Engineering, University of Rochester, Rochester, USA;

关键词: Perivascular space;    Periarterial space;    Cerebrospinal fluid;    Hydraulic resistance;   

DOI  :  10.1186/s12987-023-00454-z

 received in 2023-02-14, accepted in 2023-06-21,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundFlow of cerebrospinal fluid (CSF) through brain perivascular spaces (PVSs) is essential for the clearance of interstitial metabolic waste products whose accumulation and aggregation is a key mechanism of pathogenesis in many diseases. The PVS geometry has important implications for CSF flow as it affects CSF and solute transport rates. Thus, the size and shape of the perivascular spaces are essential parameters for models of CSF transport in the brain and require accurate quantification.MethodsWe segmented two-photon images of pial (surface) PVSs and the adjacent arteries and characterized their sizes and shapes of cross sections from 14 PVS segments in 9 mice. Based on the analysis, we propose an idealized model that approximates the cross-sectional size and shape of pial PVSs, closely matching their area ratios and hydraulic resistances.ResultsThe ratio of PVS-to-vessel area varies widely across the cross sections analyzed. The hydraulic resistance per unit length of the PVS scales with the PVS cross-sectional area, and we found a power-law fit that predicts resistance as a function of the area. Three idealized geometric models were compared to PVSs imaged in vivo, and their accuracy in reproducing hydraulic resistances and PVS-to-vessel area ratios were evaluated. The area ratio was obtained across different cross sections, and we found that the distribution peaks for the original PVS and its closest idealized fit (polynomial fit) were 1.12 and 1.21, respectively. The peak of the hydraulic resistance distribution is 1.73×1015\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$1.73\times 10^{15}$$\end{document} Pa  s/m5\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$^{5}$$\end{document} and 1.44×1015\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$1.44\times 10^{15}$$\end{document} Pa s/m5\documentclass[12pt]{minimal}\usepackage{amsmath}\usepackage{wasysym}\usepackage{amsfonts}\usepackage{amssymb}\usepackage{amsbsy}\usepackage{mathrsfs}\usepackage{upgreek}\setlength{\oddsidemargin}{-69pt}\begin{document}$$^{5}$$\end{document} for the segmentation and its closest idealized fit, respectively.ConclusionsPVS hydraulic resistance can be reasonably predicted as a function of the PVS area. The proposed polynomial-based fit most closely captures the shape of the PVS with respect to area ratio and hydraulic resistance. Idealized PVS shapes are convenient for modeling, which can be used to better understand how anatomical variations affect clearance and drug transport.

【 授权许可】

CC BY   
© The Author(s) 2023

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