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In vitro models of traumatic brain injury (TBI) are helping elucidate the pathobiological mechanisms responsible for dysfunction and delayed cell death after mechanical stimulation of the brain. Researchers have identified compounds that have the potential to break the chain of molecular events set in motion by traumatic injury. Ultimately, the utility of in vitro models in identifying novel therapeutics will be determined by how closely the in vitro cascades recapitulate the sequence of cellular events that play out in vivo after TBI. Herein, the major in vitro models are reviewed, and a discussion of the physical injury mechanisms and culture preparations is employed. A comparison between the efficacy of compounds tested in vitro and in vivo is presented as a critical evaluation of the fidelity of in vitro models to the complex pathobiology that is TBI. We conclude that in vitro models were greater than 88% predictive of in vivo results.
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Supplemental Text: A discussion of compounds in Table 1 that do not appear in the main text (PDF). Supplemental Movie 1: Equibiaxial stretch of cultures is achieved through deformation of the culture substrate by pulling the clamped membrane over a hollow cylinder. This video shows the dynamic deformation of a culture being injured with this model. Download movie file (AVI) Supplemental Movie 2: Propagation of evoked activity through the neural circuitry. Download movie file (AVI)