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Injury Biomechanics

The high incidence and socioeconomic consequences of traumatic brain injury (TBI) have prompted the development of many models in order to understand tissue response to physical insults. The underlying mechanisms that lead to cell dysfunction and death after a traumatic insult comprise complex molecular and biochemical events that have not been extensively modeled in isolated cells. Experimental models can best target these events by providing a controlled, reproducible mechanical insult to isolated components of the brain. Rapid, dynamic deformation, or strain, of isolated brain cells allows systematic correlation of cellular responses with mechanical parameters such as strain and loading rate. Biomechanically well-characterized models are used by our laboratory to determine both structural and functional tolerances to prescribed loading conditions and the cellular mechanisms that lead to dysfunction and death.

The tolerance of brain tissue and the individual cellular components may be dependent on several variables, including brain region, cellular orientation, and extracellular matrix. Accurately defined cell and tissue tolerances are crucial for the input and validation of computational models and subsequent design and improvement of protective components. The overall goal of this research is to systematically subject cell and tissue specimens to biomechanically well-defined inputs in order to determine injury mechanisms and develop criteria that are model-independent and based on cellular properties.

Biomechanical Forces in TBI

Biomechanics of TBI

  • Forces cause deformation of brain tissue
  • Brain tissue is most vulnerable to shear strains
  • Cell orientation to stress contributes to response

Traumatic loading to the head involves complex mechanics. Our lab has developed three custom electromechanical devices to study the responses of neural cells to mechanical insult in vitro.

1. Mechanical Stretch of Cell Cultures: Cultures plated on an elastic membrane may be rapidly deformed to assess the response to tensile loading. This model has been used to evaluate the transient alterations in neuronal membrane permeability as well as cellular energetics and viability.

Mechanical deformation of cell cultures

2. Shear Deformation of Planar Cell Cultures: The rapid acceleration of a fluid over planar cell cultures induces a uniform shear deformation to examine cell function and factors that initiate cell dysfunction. In addition, this system also integrates a custom multi-electrode array to assess changes in neuronal electrophysiological function before, during, or after shear deformation.

Shear deformation apparatus

3. Shear Deformation of 3-D Cell-Containing Matrices: The response of 3-D cellular constructs to high rate deformation can be analyzed in a more in vivo -like environment. This model can be used to study the effects of specific deformation regimes (e.g., shear and tensile loading) on cell viability and cytostructure after loading.

Shear deformation apparatus for 3-D cultures

Relevant Publications

  • Cullen, D. K. and LaPlaca, M. C. (2006). Neuronal response to high rate shear deformation depends on heterogeneity of the local strain field. Journal of Neurotrauma . (in press).
  • LaPlaca, M.C., Cullen, D.K., McLoughlin, J.J., Cargill II, R.S., (2005). High rate shear strain of three-dimensional neural cell cultures: A new in vitro traumatic brain injury model. Journal of Biomechanics . 38, 1093-1105.
  • Geddes, D.M., LaPlaca, M.C. , and Cargill, R.S. II Susceptibility of hippocampal neurons to mechanically-induced injury. Experimental Neurology. 184(1):420-7, 2003.
  • Geddes, D.M., Cargill, R.S. II and LaPlaca, M.C. Neural stretch results in transiently alterated in plasma membrane permeability that depends on strain rate and magnitude. Journal of Neurotrauma. 20(10): 1039-1049, 2003.
  • LaPlaca, Michelle C. and Thibault, Lawrence E. Dynamic Mechanical Deformation of Neurons Triggers an Acute Calcium Response and Cell Injury Involving the N -Methyl-D-Aspartate Glutamate Receptor. Journal of Neuroscience Research. 52:220-229, 1998.
  • LaPlaca, Michelle C., Lee, Virginia M.-Y., and Thibault, Lawrence E. An in vitro model of traumatic neuronal injury: loading rate dependent changes in acute cytosolic calcium and lactate dehydrogenase release. Journal of Neurotrauma. 14(6): 355-368, 1997.
  • LaPlaca, Michelle C. and Thibault, Lawrence E. An in vitro traumatic injury model to examine the response of NTera-2 neurons to a hydrodynamically-induced deformation. Annals of Biomedical Engineering. 25(4): 365-377, 1997.