From structure to mechanics: exploring the role of axons and interconnections in anisotropic behavior of brain white matter.

Abstract

According to various experimental studies, the role of axons in the brain's white matter (WM) is still a subject of debate: Is the role of axons in brain white matter (WM) limited to their functional significance, or do they also play a pivotal mechanical role in defining its anisotropic behavior? Micromechanics and computational models provide valuable tools for scientists to comprehend the underlying mechanisms of tissue behavior, taking into account the contribution of microstructures. In this review, we delve into the consideration of strain level, strain rates, and injury threshold to determine when WM should be regarded as anisotropic, as well as when the assumption of isotropy can be deemed acceptable. Additionally, we emphasize the potential mechanical significance of interconnections between glial cells-axons and glial cells-vessels. Moreover, we elucidate the directionality of WM stiffness under various loading conditions and define the possible roles of microstructural components in each scenario. Ultimately, this review aims to shed light on the significant mechanical contributions of axons in conjunction with glial cells, paving the way for the development of future multiscale models capable of predicting injuries and facilitating the discovery of applicable treatments.