A finite element model for simulating closed-head impact injury in a mouse model: implications for tau pathology in traumatic brain injury

Abstract

Traumatic brain injury (TBI) can cause neurodegenerative disease, which is sometimes characterized by tau mislocalization. The tau pathology can further lead to neurofibrillary tangles (NFTs), signs of brain axonal damage, usually found at the sulcus depth in the human brain or the corpus callosum region in the mouse brain, which are geometrically similar. By building and testing a 3D geometry model of the mouse brain, we found that the tau pathology and the axonal damage at the corpus callosum are highly correlated to its groove shape geometry. At the corpus callosum, the stress, strain, and strain rates are relatively higher than most regions in the mouse brain. The unique contact constraints of brain tissues can elevate the readings even higher. Different material properties of brain tissues are not likely to play an essential role in the elevation of stress, strain, and strain rate at the corpus callosum. Besides the corpus callosum, some other regions are also under high readings. They can have potential tau pathology in real animal studies. Together, these findings identify the mechanical relationships between tau pathology and TBI. Furthermore, it explained the geometrical reason why those regions get damaged. It also provides a possible research direction for discovering other areas with potential tau pathology. This model could be used in similar studies and be improved to be more accurate. In that way, it can reduce the usage of animal studies.