Journal of neurotrauma
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Journal of neurotrauma · Dec 2011
Simvastatin administration ameliorates neurobehavioral consequences of subarachnoid hemorrhage in the rat.
In the present study we assessed the neuroprotective effects of simvastatin in a rodent model of experimental subarachnoid hemorrhage (SAH). Based on recent data showing the role of statins not only in lowering the level of cholesterol but also in preventing cardiac and cerebrovascular damage in risk population, and in decreasing vasospasm and delayed ischemia after aneurysmal SAH, we investigated the neuroprotective effects of intraperitoneal administration of simvastatin (40 mg/kg/day for 5 consecutive days) in Sprague-Dawley rats 30 min after SAH, as compared to vehicle-treated SAH animals. ⋯ On days 1-4 post-SAH, simvastatin-treated rats have significantly improved beam balance scores (days 1-2, p<0.001; days 3-4, p<0.01), beam balance times (days 1-4, p<0.01), and latency to traverse the beam (days 1-3, p<0.01; day 2, p<0.005; day 4, p<0.0001) in comparison with control groups that, conversely, were not protected against SAH-related body weight changes. These results demonstrate that the administration of simvastatin may represent a beneficial therapeutic approach able to reduce post-SAH cognitive dysfunction.
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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
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 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.
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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.