The primary responsibility of the Biomechanics Core is to provide more consistent and comparable experimental models of gray matter (mouse controlled cortical impact), white matter (inertial injury in minipig, mouse optic nerve stretch), and mixed (rat lateral fluid percussion) traumatic brain injury. Our overall hypotheses for the core activities are (1) primary axonal damage is related to the tensile strain directed along the neural tracts during injury (3) injury thresholds for primary neuronal vascular, and axonal pathologies are constant across species (4) physical differences in the tissue, skull, and brain geometry across species and strains within a species can affect the injury pattern caused by a mechanical insult. The specific responsibilities of this core are: Responsibility 1: To develop and rigorously validate biomechanical models of the cortical impact technique for producing predominantly gray matter injury of programmable severity in the mouse. Responsibility 2: To use biomechanical modeling tools to correlate immunohistochemical markers for axonal damage (NF68, APP), cytoskeletal changes (SBP), and neurodegeneration (Abeta) that occur in the inertial injury in the miniature pig. Responsibility 3: Provide a model of white matter injury in the mouse optic nerve that consistently produces axonal damage in the nerve at a fixed stretch level (Year 1) an can be adjusted to provide more mild or severe levels of axonal damage (Years 2-3). Responsibility 4: Formulate, validate, and apply microstructure and molecular based models of material behavior to study the white matter (diffuse) injury models. By focusing on these responsibilities, we expect to achieve consistent and reproducible models of an injury specific pathology, understand the transfer of these models across species, and develop validated mathematical descriptions for the transfer of bulk stress and strain to the cell and molecular level. Once accomplished, the core activities will provide more powerful and standardized models to study the mechanisms, molecular sequelae, and treatment of the brain injury.
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