Traumatic Brain Injury and the Neuronal Microenvironment: A Potential Role for Neuropathological Mechanotransduction

Traumatic brain injury (TBI) is linked to several pathologies for which there is a lack of understanding of disease mechanisms and therapeutic strategies. To elucidate injury mechanisms, it is important to consider how physical forces are transmitted and transduced across all spatial scales of the brain. Although the mechanical response of the brain is typically characterized by its material properties and biological structure, cellular mechanotransduction mechanisms also exist. Such mechanisms can affect physiological processes by responding to exogenous mechanical forces directed through sub-cellular components, such as extracellular matrix and cell adhesion molecules, to mechanosensitive intracellular structures that regulate mechanochemical signaling pathways. We suggest that cellular mechanotransduction may be an important mechanism underlying the initiation of cell and sub-cellular injuries ultimately responsible for the diffuse pathological damage and clinical symptoms observed in TBI, thereby providing potential therapeutic opportunities not previously explored in TBI.