Journal of neurotrauma
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Journal of neurotrauma · Sep 2013
17β-estradiol confers protection after traumatic brain injury in the rat and involves activation of g protein-coupled estrogen receptor 1.
Abstract Traumatic brain injury (TBI) is a significant public health problem in the United States. Despite preclinical success of various drugs, to date all clinical trials investigating potential therapeutics have failed. Recently, sex steroid hormones have sparked interest as possible neuroprotective agents after traumatic injury. ⋯ We also report a significant reduction in astrogliosis in the ipsilateral cortex, hilus, and CA 2/3 region of the hippocampus. Finally, these effects were observed to be chiefly dose-dependent for E2, with the 5 mg/kg dose generating a more robust level of protection. Our findings further elucidate estrogenic compounds as a clinically relevant pharmacotherapeutic strategy for treatment of secondary injury following TBI, and intriguingly, reveal a novel potential therapeutic target in GPER.
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Journal of neurotrauma · Sep 2013
Long-term in vivo imaging of viscoelastic properties of the mouse brain after controlled cortical impact.
Traumatic brain injury (TBI) presents a variety of causes and symptoms, thus making the development of reliable diagnostic methods and therapeutic treatments challenging. Magnetic resonance elastography (MRE) is a technique that allows for a noninvasive assessment of the mechanical properties of soft biological tissue, such as tissue stiffness, storage modulus, and loss modulus. Importantly, by quantifying the changes in the stiffness of tissue that is often associated with disease, MRE is able to detect tissue pathologies at early stages. ⋯ For both groups, we observed a significant drop in the stiffness of the impacted region immediately following the injury; the 0.75 mm animals experienced increased tissue softness that lasted longer than that for the 0.5 mm group. Although the shear stiffness, storage modulus, and loss modulus parameters all followed the same trend, the tissue stiffness yielded the most statistically significant results. Overall, this article introduces a transformative technique for mechanically mapping the brain and detecting brain diseases and injury.
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Journal of neurotrauma · Sep 2013
Dose- and Time-Dependent Neuroprotective Effects of Pycnogenol(®) following Traumatic Brain Injury.
After traumatic brain injury (TBI), both primary and secondary injury cascades are initiated, leading to neuronal death and cognitive dysfunction. We have previously shown that the combinational bioflavonoid, Pycnogenol (PYC), alters some secondary injury cascades and protects synaptic proteins when administered immediately following trauma. The purpose of the present study was to explore further the beneficial effects of PYC and to test whether it can be used in a more clinically relevant fashion. ⋯ PYC treatment significantly protected both the cortex and hippocampus from injury-related declines in pre- and post-synaptic proteins. These results demonstrate that a single i.v. treatment of PYC is neuroprotective after TBI with a therapeutic window of at least 4 h post trauma. The natural bioflavonoid PYC may provide a possible therapeutic intervention in neurotrauma.
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Journal of neurotrauma · Sep 2013
Why Is CA3 More Vulnerable Than CA1 in Experimental Models of Controlled Cortical Impact-Induced Brain Injury?
One interesting finding of controlled cortical impact (CCI) experiments is that the CA3 region of the hippocampus, which is positioned further from the impact than the CA1 region, is reported as being more injured. The current literature has suggested a positive correlation between brain tissue stretch and neuronal cell loss. However, it is counterintuitive to assume that CA3 is stretched more during CCI injury. ⋯ Simulation results demonstrated that for CCI with a 5-mm diameter, flat shape impactor, CA3 experienced increased tensile strains over a larger area and to a greater magnitude than did CA1 for group 1, which best explained why CA3 is more sensitive to CCI injury. However, for groups 2-4, the total volume with high strain (>30%) in CA3 was smaller than that in CA1. The FE rat brain model, with detailed hippocampal structures presented here, will help to engineer desired experimental neurotrauma models by virtually characterizing brain biomechanics before testing.
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Journal of neurotrauma · Sep 2013
Randomized Controlled Trial Multicenter StudyNeurological Outcome Scale for Traumatic Brain Injury: III. Criterion-Related Validity and Sensitivity to Change in the NABIS Hypothermia-II Clinical Trial.
The neurological outcome scale for traumatic brain injury (NOS-TBI) is a measure assessing neurological functioning in patients with TBI. We hypothesized that the NOS-TBI would exhibit adequate concurrent and predictive validity and demonstrate more sensitivity to change, compared with other well-established outcome measures. We analyzed data from the National Acute Brain Injury Study: Hypothermia-II clinical trial. ⋯ The NOS-TBI demonstrated higher sensitivity to change, compared with the GOS (p<0.038) and GOS-E (p<0.016). In summary, the NOS-TBI demonstrated adequate concurrent and predictive validity as well as sensitivity to change, compared with gold-standard outcome measures. The NOS-TBI may enhance prediction of outcome in clinical practice and measurement of outcome in TBI research.