Modeling traumatic brain injury in vitro: Functional changes in the absence of cell death

Traumatic brain injury (TBI) is caused by in response to mechanical loading of the head. An extended biological cascade is initiated by the deformation and results in delayed cell death and dysfunction. Using an in vitro model of TBI based on organotypic brain slice cultures, we have quantitatively studied the relationship between tissue deformation and outcome. In the current study, we asked the question whether low levels of tissue strain would affect brain tissue function as measured by electrophysiological recordings. In response to 5% and 10% biaxial Lagrangian strain the maximal evoked response was decreased and the current to elicit a half maximal response was increased. These results indicate that less neurons were firing in response to an electrical stimulus and that they were less excitable. These results suggest that functional alterations of neuronal networks occurs at lower strains than those required to induce cell death.