The mechanical importance of myelination in the central nervous system.

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±0.20kPa pre-natally to 0.68±0.20kPa post-natally; the white matter stiffness tripled from 0.45±0.18kPa pre-natally to 1.33±0.64kPa 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.