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Injury Response

Fig. 1. Steps in CNS trauma. Traumatic brain and spinal cord injuries result from mechanical loading to the tissue. Pathophysiological events are initiated by the mechanical tissue response to impact.

secondary response primary response lifespan

Fig. 2. Temporal aspects of injury. Mechanical loading causes an acute primary phase followed by a prolonged secondary phase. The primary response is characterized by nonspecific cell loss, which initiates a cascade of complex secondary events such as inflammation, excitotoxicity, and neurodegeneration.

A notable application of the study of biomechanics in CNS trauma is the determination of accurate tissue tolerances. Tissue tolerances are defined as the point at which structural and/or physiological failure occurs. An improved understanding of injury biomechanics and the resulting brain and spinal cord responses will ultimately facilitate the development of improved protective gear (e.g., helmets and seat belts). Determination of tolerance criteria requires information about the forces and deformations that lead to failure, but the mechanical parameters (i.e., magnitude and rate of force and deformation) are only partially understood. Tissue response and tolerance criteria for humans are largely based on cadaveric studies, but may not accurately represent the properties of living tissue. Basic cell and animal studies, in which a defined mechanical insult can be applied to live cells in culture or in an intact animal, have an advantage for the determination of tissue tolerance and may lead to the refinement of human tolerance criteria. These tolerance criteria must be model-independent and represent inherent system properties.

We will discuss basic biomechanical concepts as they relate to traumatic brain and spinal cord injuries and present experimental models that have been developed and characterized in an attempt to mimic the forces and deformations occurring in human CNS trauma. The mechanisms by which the mechanical response to a traumatic insult leads to dysfunction are complex, yet can be simplified using controlled cellular injury models that account for deformation magnitude and rate. Bio-mechanically relevant in vitro TBI models, used in combination with animal studies and computer simulations, may lead to improved cellular and tissue injury tolerance criteria as well as a more complete understanding of the relationship between the biomechanical input and pathophysio-logical changes. This multilevel approach will be discussed with respect to selection of experimental models, development of mechanistically driven treatment strategies, and future research priorities.

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