Journal of neurotrauma
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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.
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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
Comparative StudyLive imaging of axon stretch growth in embryonic and adult neurons.
Strategies for nervous system repair arise from knowledge of growth mechanisms via a growth cone. The distinctive process of axon stretch growth is a robust, long-term growth that may reveal new pathways to accelerate nerve repair. Here, a live imaging bioreactor was engineered to closely explore cellular events initiated by applied tension. ⋯ Surprisingly, axons recovered and were capable of subsequent stretch growth. When tension was completely released (?5% strain), stretch grown axons retracted at rates up to 6.1??m/sec and slowed as resting tension was restored. This ability to assess the process of axon stretch growth in real time will allow detailed study of how tension can be used to drive axonal growth and retraction.