The Underestimated Role of Mechanical Stimuli in Brain Diseases and the Related In Vitro Models

Background: Besides the well-documented biochemical and electrophysiological effects, the mechanical stimuli also have prominent roles in the initiation and development of brain diseases but yet have been under-estimated. To explore the role of mechanical stimuli and the followed mechanical-biochemical effects in the brain diseases. Method: In this review, we discussed the initiation and effect of mechanical stimuli and the surrounding topography in brain diseases, especially for the intracerebral hemorrhage (ICH), Alzheimer's disease (AD), diffuse axonal injury (DAI) and primary brain tumors. The induced cascades of biological pathways by mechanical stimuli prior to and during the brain diseases were summarized. Strategies aiming to reduce the mechanical stimuli related damages or poor outcomes were also discussed, despite some could only prevent rather than cure. Literatures have indicated mechanical stimuli were the connection between the exogenous mechanotransduction and the inherent biochemical cascades. Therefore, we also reviewed in vitro models in the literatures that simulated the diverse range of mechanical stimuli, which connected the neural network with the tissue engineering, biomaterials and potential therapeutic strategies together. Results: At the microscopic and macroscopic levels, the hydrostatic pressure, tensile/compressive force, shear force, and even the roughness of topography from the physical surrounding exert the influence on the neural network not only by themselves but also through the interaction with other factors, e.g. biochemical or electrophysiological effects. Conclusion: In the clinical management, taking the undervalued mechanical stimuli and the followed mechanical- biochemical effects into consideration are important and inevitable in preventing and treating brain diseases.