Journal of neurotrauma
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Journal of neurotrauma · Nov 2011
Single-walled carbon nanotubes chemically functionalized with polyethylene glycol promote tissue repair in a rat model of spinal cord injury.
Traumatic spinal cord injury (SCI) induces tissue damage and results in the formation of a cavity that inhibits axonal regrowth. Filling this cavity with a growth-permissive substrate would likely promote regeneration and repair. Single-walled carbon nanotubes functionalized with polyethylene glycol (SWNT-PEG) have been shown to increase the length of selected neurites in vitro. ⋯ We found that post-SCI administration of SWNT-PEG decreased lesion volume, increased neurofilament-positive fibers and corticospinal tract fibers in the lesion, and did not increase reactive gliosis. Additionally, post-SCI administration of SWNT-PEG induced a modest improvement in hindlimb locomotor recovery without inducing hyperalgesia. These data suggest that SWNT-PEG may be an effective material to promote axonal repair and regeneration after SCI.
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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.
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Journal of neurotrauma · Nov 2011
ReviewToward a convergence of regenerative medicine, rehabilitation, and neuroprosthetics.
No effective therapeutic interventions exist for severe neural pathologies, despite significant advances in regenerative medicine, rehabilitation, and neuroprosthetics. Our current hypothesis is that a specific combination of tissue engineering, pharmacology, cell replacement, drug delivery, and electrical stimulation, together with plasticity-promoting and locomotor training (neurorehabilitation) is necessary to interact synergistically in order to activate and enable all damaged circuits. ⋯ Therefore, the objective of this review is to highlight the convergent themes, which we believe have a common goal of restoring function after neural damage. The convergent themes discussed in this review include modulation of inflammation and secondary damage, encouraging endogenous repair/regeneration (using scaffolds, cell transplantation, and drug delivery), application of electrical fields to modulate healing and/or activity, and finally modulation of plasticity.
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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.