Journal of neurotrauma
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Increased intracranial pressure (ICP) caused by edema following severe traumatic brain injury (TBI) or stroke contributes to high rates of mortality and morbidity. The search continues for more effective treatments that target the edema that contributes to increased ICP. We previously described the effect of the fixed charge density (FCD) of brain on its swelling behavior according to the Donnan effect. ⋯ ChABC reduced swelling in live slices of tissue even within the first 2?h following dissection. It also significantly reduced the FCD, initial tissue swelling, and volume change in response to hypotonic bathing solution in porcine cortical brain tissue. The use of ChABC to reduce tissue FCD may be an effective method for reducing brain edema and controlling ICP following injury.
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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
Case Reports Comparative StudyComparison of acute and chronic traumatic brain injury using semi-automatic multimodal segmentation of MR volumes.
Although neuroimaging is essential for prompt and proper management of traumatic brain injury (TBI), there is a regrettable and acute lack of robust methods for the visualization and assessment of TBI pathophysiology, especially for of the purpose of improving clinical outcome metrics. Until now, the application of automatic segmentation algorithms to TBI in a clinical setting has remained an elusive goal because existing methods have, for the most part, been insufficiently robust to faithfully capture TBI-related changes in brain anatomy. This article introduces and illustrates the combined use of multimodal TBI segmentation and time point comparison using 3D Slicer, a widely-used software environment whose TBI data processing solutions are openly available. ⋯ The proposed tools allow cross-correlation of multimodal metrics from structural imaging (e.g., structural volume, atrophy measurements) with clinical outcome variables and other potential factors predictive of recovery. In addition, the workflows described are suitable for TBI clinical practice and patient monitoring, particularly for assessing damage extent and for the measurement of neuroanatomical change over time. With knowledge of general location, extent, and degree of change, such metrics can be associated with clinical measures and subsequently used to suggest viable treatment options.
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Journal of neurotrauma · Nov 2011
Microfluidic generation of haptotactic gradients through 3D collagen gels for enhanced neurite growth.
We adapted a microfluidic system used previously to generate durotactic gradients of stiffness in a 3D collagen gel, to produce haptotactic gradients of adhesive ligands through the collagen gel. Oligopeptide sequences that included bioactive peptide sequences from laminin, YIGSR, or IKVAV, were grafted separately onto type I collagen using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC). Solutions of peptide-grafted collagen and untreated collagen were then used as source and sink input solutions, respectively, in an H-shaped microfluidic network fabricated using traditional soft lithography. ⋯ When these two gradients were presented in combination, the bias in growth acceleration was the largest and most consistent. No differences were observed in the number of neurites choosing to grow up or down the gradients in any condition. These results suggest that the incorporation of distinct gradients of multiple bioactive ligands can improve directional acceleration of regenerating axons.
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Journal of neurotrauma · Nov 2011
Comparative StudyEngineered in vitro/in silico models to examine neurite target preference.
Research on spinal cord injury (SCI) repair focuses on developing mechanisms to allow neurites to grow past an injury site. In this article, we observe that numerous divergent paths (i.e., spinal roots) are present along the spinal column, and hence guidance strategies must be devised to ensure that regrowing neurites reach viable targets. ⋯ We find in both in silico and in vitro models that the probability of a neurite entering a given root decreases exponentially with respect to the number of roots away from the DRG; consequently, the likelihood of neurites reaching a distant root can be vanishingly small. This result represents a starting point for future strategies to optimize the likelihood that neurites will reach appropriate targets in the regenerating nervous system, and provides a new computational tool to evaluate the feasibility and expected success of neurite guidance in complex geometries.