Journal of neurotrauma
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Journal of neurotrauma · Nov 2011
Comparative StudyA detailed viscoelastic characterization of the P17 and adult rat brain.
Brain is a morphologically and mechanically heterogeneous organ. Although rat brain is commonly used as an experimental neurophysiological model for various in vivo biomechanical studies, little is known about its regional viscoelastic properties. To address this issue, we have generated viscoelastic mechanical property data for specific anatomical regions of the P17 and adult rat brain. ⋯ All models fit the data equally with no significant differences between them (F-test; p>0.05). The F-test was also used to statistically determine that a Prony series with three time-dependent parameters accurately fit the data with no added benefit from additional terms. The age- and region-dependent rat brain viscoelastic properties presented here will help inform future biomechanical models of the rat brain with specific and accurate regional mechanical property data.
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Several key biological mechanisms of traumatic injury to axons have been elucidated using in vitro stretch injury models. These models, however, are based on the experimentation of single cultures keeping productivity slow. Indeed, low yield has hindered important and well-founded investigations requiring high throughput methods such as proteomic analyses. ⋯ Data also confirmed that the pressure pulse was distributed evenly throughout the pressure chambers and therefore to each injury well. Importantly, the relationship between substrate deformation and applied pressure was consistent among the multiple wells and displayed a predictable linear behavior in each module. These data confirm that this multi-well system performs as well as currently used stretch injury devices and can undertake high throughput studies that are needed across the field of neurotrauma research.
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Journal of neurotrauma · Nov 2011
Trauma-induced plasmalemma disruptions in three-dimensional neural cultures are dependent on strain modality and rate.
Traumatic brain injury (TBI) results from cell dysfunction or death following supra-threshold physical loading. Neural plasmalemma compromise has been observed following traumatic neural insults; however, the biomechanical thresholds and time-course of such disruptions remain poorly understood. In order to investigate trauma-induced membrane disruptions, we induced dynamic strain fields (0.50 shear or compressive strain at 1, 10, or 30?sec(?1) strain rate) in 3-D neuronal-astrocytic co-cultures (>500??m thick). ⋯ At 48?h post-insult, cell death increased significantly in the high-strain-rate group, but not after quasi-static loading, suggesting that cell survival relates to the initial extent of transient structural compromise. Cells were more sensitive to bulk shear deformation than compression with respect to acute permeability changes and subsequent cell survival. These results provide insight into the temporally varying alterations in membrane stability following traumatic loading and provide a basis for elucidating physical cellular tolerances.
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Journal of neurotrauma · Nov 2011
Comparative StudyStrain-based regional traumatic brain injury intensity in controlled cortical impact: a systematic numerical analysis.
Regional strain-based brain injury intensity during controlled cortical impact (CCI) was studied using a three-dimensional numerical rat brain model. A full factorial design of CCI computer experiments was performed using two typical impactor shapes (flat or hemispherical) at a fixed impact velocity of 4?m/s with various impact depths (1, 1.5, 1.6, 2, 2.5, 2.7, and 3?mm) and various impactor diameters (4, 5, 6, 8, and 9.5?mm). In total, 70 CCI cases were simulated numerically. ⋯ For the flat impactor group, the 5?mm diameter impactor induced more tissue strain in the corpus callosum/hippocampus, and a smaller impactor induced more strain in the thalamus. For the hemispherical impactor group, a larger impactor tended to induce more tissue strain in subcortical regions, with the exception of the 6?mm diameter impactor. This study systematically predicts regional intensity of primary brain injury according to tissue strain distributions in the hope that strain distribution maps may become a common platform to compare CCI severities with different configurations.
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Journal of neurotrauma · Nov 2011
Rate of neurodegeneration in the mouse controlled cortical impact model is influenced by impactor tip shape: implications for mechanistic and therapeutic studies.
Controlled cortical impact (CCI), one of the most common models of traumatic brain injury, is being increasingly used with mice for exploration of cell injury mechanisms and pre-clinical evaluation of therapeutic strategies. Although CCI brain injury was originally effected using an impactor with a rounded tip, the majority of studies with mouse CCI use a flat or beveled tip. Recent finite element modeling analyses demonstrate that tip geometry is a significant determinant of predicted cortical tissue strains in rat CCI, and that cell death is proportional to predicted tissue strains. ⋯ The flat-tip impactor was associated in general with more regional hippocampal neurodegeneration, especially at early time points such as 4?h. Impactor tip geometry did not have a notable effect on blood?brain barrier breakdown, traumatic axonal injury, or motor and cognitive dysfunction. Execution of CCI injury with a rounded-tip impactor is posited to provide a substantially enhanced temporal window for the study of cellular injury mechanisms and therapeutic intervention while maintaining critical aspects of the pathophysiological response to contusion brain injury.