TY - JOUR
T1 - The mechanical importance of myelination in the central nervous system
AU - Weickenmeier, Johannes
AU - de Rooij, Rijk
AU - Budday, Silvia
AU - Ovaert, Timothy C.
AU - Kuhl, Ellen
N1 - Publisher Copyright:
© 2017 Elsevier Ltd
PY - 2017/12
Y1 - 2017/12
N2 - Neurons in the central nervous system are surrounded and cross-linked by myelin, a fatty white substance that wraps around axons to create an electrically insulating layer. The electrical function of myelin is widely recognized; yet, its mechanical importance remains underestimated. Here we combined nanoindentation testing and histological staining to correlate brain stiffness to the degree of myelination in immature, pre-natal brains and mature, post-natal brains. We found that both gray and white matter tissue stiffened significantly (p≪0.001) upon maturation: the gray matter stiffness doubled from 0.31±0.20 kPa pre-natally to 0.68±0.20 kPa post-natally; the white matter stiffness tripled from 0.45±0.18 kPa pre-natally to 1.33±0.64 kPa post-natally. At the same time, the white matter myelin content increased significantly (p≪0.001) from 58±2% to 74±9%. White matter stiffness and myelin content were correlated with a Pearson correlation coefficient of ρ=0.92 (p≪0.001). Our study suggests that myelin is not only important to ensure smooth electrical signal propagation in neurons, but also to protect neurons against physical forces and provide a strong microstructural network that stiffens the white matter tissue as a whole. Our results suggest that brain tissue stiffness could serve as a biomarker for multiple sclerosis and other forms of demyelinating disorders. Understanding how tissue maturation translates into changes in mechanical properties and knowing the precise brain stiffness at different stages of life has important medical implications in development, aging, and neurodegeneration.
AB - Neurons in the central nervous system are surrounded and cross-linked by myelin, a fatty white substance that wraps around axons to create an electrically insulating layer. The electrical function of myelin is widely recognized; yet, its mechanical importance remains underestimated. Here we combined nanoindentation testing and histological staining to correlate brain stiffness to the degree of myelination in immature, pre-natal brains and mature, post-natal brains. We found that both gray and white matter tissue stiffened significantly (p≪0.001) upon maturation: the gray matter stiffness doubled from 0.31±0.20 kPa pre-natally to 0.68±0.20 kPa post-natally; the white matter stiffness tripled from 0.45±0.18 kPa pre-natally to 1.33±0.64 kPa post-natally. At the same time, the white matter myelin content increased significantly (p≪0.001) from 58±2% to 74±9%. White matter stiffness and myelin content were correlated with a Pearson correlation coefficient of ρ=0.92 (p≪0.001). Our study suggests that myelin is not only important to ensure smooth electrical signal propagation in neurons, but also to protect neurons against physical forces and provide a strong microstructural network that stiffens the white matter tissue as a whole. Our results suggest that brain tissue stiffness could serve as a biomarker for multiple sclerosis and other forms of demyelinating disorders. Understanding how tissue maturation translates into changes in mechanical properties and knowing the precise brain stiffness at different stages of life has important medical implications in development, aging, and neurodegeneration.
KW - Brain
KW - Indentation
KW - Myelin
KW - Myelination
KW - Stiffness
KW - White matter
UR - http://www.scopus.com/inward/record.url?scp=85018757426&partnerID=8YFLogxK
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U2 - 10.1016/j.jmbbm.2017.04.017
DO - 10.1016/j.jmbbm.2017.04.017
M3 - Article
C2 - 28462864
AN - SCOPUS:85018757426
SN - 1751-6161
VL - 76
SP - 119
EP - 124
JO - Journal of the Mechanical Behavior of Biomedical Materials
JF - Journal of the Mechanical Behavior of Biomedical Materials
ER -