Journal of neurotrauma
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Journal of neurotrauma · Oct 2015
Characterization of Subcellular Responses Induced by Exposure of Microbubbles to Astrocytes.
Blast traumatic brain injury (bTBI) has now been identified to associate with adverse health consequences among combat veterans. Post-traumatic stress disorder linked with explosive blasts, for example, may result from such brain injury. The fundamental questions about the nature, diagnosis, and long-term consequences of bTBI and causative relationship to post-traumatic stress disorder remain elusive, however. ⋯ Of the cells that survived the initial assault, several subcellular changes were monitored and determined using fluorescent microscopy, including cell viability, cytoskeletal reorganization, changes in focal adhesion, membrane permeability, and potential onset of apoptosis. While the astrocytes impacted by the shock wave only demonstrated essentially unaltered cellular behavior, the astrocytes exposed to microbubbles exhibited significantly different responses, including production of reactive oxygen species by collapse of microbubbles. In the present study, we characterized and report for the first time the altered biophysical and subcellular properties in astrocytes in response to exposure to the combination of shock waves and microbubbles.
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Journal of neurotrauma · Oct 2015
Studying axonal outgrowth and regeneration of the corticospinal tract in organotypic slice cultures.
Studies of axonal outgrowth and regeneration after spinal cord injury are hampered by the complexity of the events involved. Here, we present a simple and improved in vitro approach to investigate outgrowth, regeneration of the corticospinal tract, and intrinsic parenchymal responses. ⋯ Our data show that: a) motor-cortical outgrowth is already detectable after 1 d in culture and is source specific; b) treatment with neurotrophin-3 and C3 transferase from Clostridium botulinum significantly enhances axonal outgrowth during the course of cultivation; c) outgrowing axons form synaptic connections, as demonstrated by immunohistochemistry and calcium imaging; and d) migrating cells of motor-cortical origin can be reliably identified without previous tracing and are mostly neural precursors that survive and mature in the spinal cord parenchyma. Thus, our model is suitable for screening for candidate substances that enhance outgrowth and regeneration of the corticospinal tract and for studying the role of endogenous neural precursors after lesion induction.
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Journal of neurotrauma · Oct 2015
MEG Slow-wave Detection in Patients with Mild Traumatic Brain Injury and Ongoing Symptoms Correlated with Long-Term Neuropsychological Outcome.
Mild traumatic brain injury (mTBI) is common in the United States, accounting for as many as 75-80% of all TBIs. It is recognized as a significant public health concern, but there are ongoing controversies regarding the etiology of persistent symptoms post-mTBI. This constellation of nonspecific symptoms is referred to as postconcussive syndrome (PCS). ⋯ In addition, significant correlations between slow-wave activity on MEG and patterns of cognitive functioning were found in cortical areas, consistent with cognitive impairments on exams. Results provide more objective evidence that there may be subtle changes to the neurobiological integrity of the brain that can be detected by MEG. Further, these findings suggest that these abnormalities are associated with cognitive outcomes and may account, at least in part, for long-term PCS in those who have sustained an mTBI.
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Journal of neurotrauma · Sep 2015
Alteration of resting-state brain sensorimotor connectivity following spinal cord injury: A resting-state fMRI study.
Motor and sensory deficits after spinal cord injury (SCI) result in functional reorganization of the sensorimotor network. While several task-evoked functional magnetic resonance imaging (fMRI) studies demonstrated functional alteration of the sensorimotor network in SCI, there has been no study of the possible alteration of resting-state functional connectivity using resting-state fMRI. The aim of this study was to investigate the changes of brain functional connectivity in the sensorimotor cortex of patients with SCI. ⋯ Our findings demonstrated that, compared with control subjects, patients with SCI showed increased functional connectivity between primary motor cortex and other motor areas, such as the supplementary motor area and basal ganglia. However, decreased functional connectivity between primary somatosensory cortex and secondary somatosensory cortex also was found in patients with SCI, compared with controls. These findings therefore demonstrated alteration of the resting-state sensorimotor network in patients with SCI, who showed increased connectivity between motor components, and decreased connectivity between sensory components, within the sensorimotor network, suggesting that motor components within the motor network increased in functional connectivity in order to compensate for motor deficits, whereas the sensory network did not show any such increases or compensation for sensory deficits.
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Journal of neurotrauma · Sep 2015
Nanoparticle Estrogen in Rat Spinal Cord Injury Elicits Rapid Anti-inflammatory Effects in Plasma, CSF and Tissue.
Persons with spinal cord injury (SCI) are in need of effective therapeutics. Estrogen (E2), as a steroid hormone, is a highly pleiotropic agent; with anti-inflammatory, anti-apoptotic, and neurotrophic properties, it is ideal for use in treatment of patients with SCI. Safety concerns around the use of high doses of E2 have limited clinical application, however. ⋯ E2 showed rapid anti-inflammatory effects, significantly reducing interleukin (IL)-6, GRO-KC, MCP-1, and S100β in one or all compartments. Numerous additional targets of rapid E2 modulation were identified including: leptin, MIP-1α, IL-4, IL-2, IL-10, IFNγ, tumor necrosis factor-α, etc. These data further elucidate the rapid anti-inflammatory effects E2 exerts in an acute rat SCI model, have identified additional targets of estrogen efficacy, and suggest nanoparticle delivered estrogen may provide a safe and efficacious treatment option in persons with acute SCI.