The soft mechanical signature of glial scars in the central nervous system

Moeendarbary, Emad; Weber, Isabell P.; Sheridan, Graham K.; Koser, David E.; Soleman, Sara; Haenzi, Barbara; Bradbury, Elizabeth J.; Fawcett, James W.; Franze, Kristian

doi:10.1038/ncomms14787

Cited by 304 publications

(326 citation statements)

References 62 publications

(104 reference statements)

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“…The overall elastic stiffness of retinal tissue measured in this study was comparable to that of other CNS tissues assessed by AFM (6, 8–11, 47, 50–52). Similarly, the Brillouin shifts we measured in the retina are comparable with values published in previous literature (18, 20, 21).…”

Section: Discussionsupporting

confidence: 72%

The role of cell body density in ruminant retina mechanics assessed by atomic force and Brillouin microscopy

et al. 2017

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Cells in the central nervous system (CNS) respond to the stiffness of their environment. CNS tissue is mechanically highly heterogeneous, thus providing motile cells with region-specific mechanical signals. While CNS mechanics has been measured with a variety of techniques, reported values of tissue stiffness vary greatly, and the morphological structures underlying spatial changes in tissue stiffness remain poorly understood. We here exploited two complementary techniques, contact-based atomic force microscopy and contact-free Brillouin microscopy, to determine the mechanical properties of ruminant retinae, which are built up by different tissue layers. As in all vertebrate retinae, layers of high cell body densities (‘nuclear layers’) alternate with layers of low cell body densities (‘plexiform layers’). Different tissue layers varied significantly in their mechanical properties, with the photoreceptor layer being the stiffest region of the retina, and the inner plexiform layer belonging to the softest regions. As both techniques yielded similar results, our measurements allowed us to calibrate the Brillouin microscopy measurements and convert the Brillouin shift into a quantitative assessment of elastic tissue stiffness with optical resolution. Similar as in the mouse spinal cord and the developing Xenopus brain, we found a strong correlation between nuclear densities and tissue stiffness. Hence, the cellular composition of retinae appears to strongly contribute to local tissue stiffness, and Brillouin microscopy shows a great potential for the application in vivo to measure the mechanical properties of transparent tissues.

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Section: Discussionsupporting

confidence: 72%

The role of cell body density in ruminant retina mechanics assessed by atomic force and Brillouin microscopy

et al. 2017

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“…Brain mechanical properties influence many vital neurological functions including brain development, metabolism, and tissue repair . However, studying brain mechanical properties in a noninvasive fashion encounters a number of challenges including the fact that the brain is protected by the skull as well as the heterogeneous and complex geometry of the brain .…”

Section: Introductionmentioning

confidence: 99%

Fast tomoelastography of the mouse brain by multifrequency single‐shot MR elastography

Bertalan

Guo

Tzschätzsch

et al. 2018

Magnetic Resonance in Med

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Purpose To introduce in vivo multifrequency single‐shot magnetic resonance elastography for full‐FOV stiffness mapping of the mouse brain and to compare in vivo stiffness of neural tissues with different white‐to‐gray matter ratios. Methods Viscous phantoms and 10 C57BL‐6 mice were investigated by 7T small‐animal MRI using a single‐shot spin‐echo planar imaging magnetic resonance elastography sequence with motion‐encoding gradients positioned before the refocusing pulse. Wave images were acquired over 10 minutes for 6 mechanical vibration frequencies between 900 and 1400 Hz. Stiffness maps of shear wave speed (SWS) were computed using tomoelastography data processing and compared with algebraic Helmholtz inversion (AHI) for signal‐to‐noise ratio (SNR) analysis. Different brain regions were analyzed including cerebral cortex, corpus callosum, hippocampus, and diencephalon. Results In phantoms, algebraic Helmholtz inversion–based SWS was systematically biased by noise and discretization, whereas tomoelastography‐derived SWS was consistent over the full SNR range analyzed. Mean in vivo SWS of the whole brain was 3.76 ± 0.33 m/s with significant regional variation (hippocampus = 4.91 ± 0.49 m/s, diencephalon = 4.78 ± 0.78 m/s, cerebral cortex = 3.53 ± 0.29 m/s, and corpus callosum = 2.89 ± 0.17 m/s). Conclusion Tomoelastography retrieves mouse brain stiffness within shorter scan times and with greater detail resolution than classical algebraic Helmholtz inversion–based magnetic resonance elastography. The range of SWS values obtained here indicates that mouse white matter is softer than gray matter at the frequencies investigated.

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“…The composition of the brain ECM is important in the injury response; whilst scar tissue in most regions of the body (i.e., skin, heart, muscle) is typically stiffer than the surrounding healthy tissue, the glial scar is actually softer than healthy tissue. This may be partly due to the lack of fibrous collagen type I in the brain (Moeendarbary et al, 2017).…”

Section: Materials Properties Of the Brainmentioning

confidence: 99%