Journal of neurotrauma
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Journal of neurotrauma · Jun 2008
Characterizing white matter damage in rat spinal cord with quantitative MRI and histology.
ABSTRACT Diffusion tensor imaging (DTI) and quantitative T(2) magnetic resonance imaging (MRI) were used to characterize ex vivo the white matter damage at 3 and 8 weeks following dorsal column transection (DC Tx) injury at the cervical level C5 of rat spinal cords. Luxol Fast Blue (LFB) and myelin basic protein (MBP) staining was used to assess myelin damage, and neurofilament-H in combination with neuron specific beta-III-tubulin (NF/Tub) staining was used to assess axonal damage. Average values of myelin water fraction (MWF), fractional anisotropy (FA), longitudinal diffusivity (D(long)), transverse diffusivity (D(trans)), and average diffusivity (D(ave)) were calculated in the fasciculus gracilis, fasciculus cuneatus, and the dorsal corticospinal tract (CST) 5 mm cranial, as well as 5 and 10 mm caudal to injury and correlated with histology. ⋯ Both MWF and D(trans) showed significant correlation with LFB staining at 3 weeks (0.64 and -0.49, respectively) and 8 weeks post-injury (0.88 and -0.71, respectively). Both D(long) and FA correlated significantly with NF/Tub staining at 3 weeks post-injury (0.78 and 0.64, respectively), while only D(long) displayed significant correlation 8 weeks post-injury (0.58 and 0.33, respectively). This study demonstrates that quantitative MRI can accurately characterize white matter damage in DC Tx model of injury in rat spinal cord.
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Journal of neurotrauma · Jun 2008
Effects of Glasgow Outcome Scale misclassification on traumatic brain injury clinical trials.
The Glasgow Outcome Scale (GOS) is the primary endpoint for efficacy analysis of clinical trials in traumatic brain injury (TBI). Accurate and consistent assessment of outcome after TBI is essential to the evaluation of treatment results, particularly in the context of multicenter studies and trials. The inconsistent measurement or interobserver variation on GOS outcome, or for that matter, on any outcome scales, may adversely affect the sensitivity to detect treatment effects in clinical trial. ⋯ The magnitude of such influence not only depends on the size of the misclassification, but also on the magnitude of the treatment effect. In conclusion, nondifferential misclassification directly reduces the power of finding the true treatment effect. An awareness of this procedural error and methods to reduce misclassification should be incorporated in TBI clinical trials.
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Journal of neurotrauma · Jun 2008
Efficacy of progesterone following a moderate unilateral cortical contusion injury.
Traumatic brain injury (TBI) results in an accumulation of edema and loss of brain tissue. Progesterone (PROG) has been reported to reduce edema and cortical tissue loss in a bilateral prefrontal cortex injury. This study tests the hypothesis that PROG is neuroprotective following a unilateral parietal cortical contusion injury (CCI). ⋯ Group IV received two additional injections (4 mg/kg on day 5; 2 mg/kg on day 6). PROG failed to alter both cortical edema and tissue sparing at any dose. Failure to modify two major sequelae associated with TBI brings into question the clinical usefulness of PROG as an effective treatment for all types of brain injury.
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Journal of neurotrauma · Jun 2008
IL-10 production is reduced by hypothermia but augmented by hyperthermia in rat microglia.
Pro-inflammatory cytokines and nitric oxide (NO) are considered responsible for exacerbating brain injury. Activated microglia produce these potentially cytotoxic factors during neuron destruction. The beneficial effects of hypothermia on neuroprotection are considered to be due, in part, to suppression of post-injury inflammatory factors by microglia. ⋯ In this study, hypothermia reduced production of IL-6, IL-10, and NO by LPS-activated microglia, suggesting that the neuroprotective effects of hypothermia might involve not only the inhibition of inflammatory factors, but also anti-inflammatory factor(s). Hyperthermia specifically increased IL-10 production in these cells. These temperature-dependent changes in IL-10 production may imply an important clinical marker for this cytokine in hypothermia-related neuronal protection and in hyperthermia-related neuronal injury.
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Journal of neurotrauma · Jun 2008
Cerebral apoptosis in severe traumatic brain injury patients: an in vitro, in vivo, and postmortem study.
One of the most important recent observations in traumatic brain injury (TBI) relates to the potential role of apoptosis in secondary brain injury. We aimed to analyze the presence of apoptosis and the expression of apoptosis-related proteins in brain samples from patients with TBI. We also tried to find any association between the in situ results and the in vitro observations in a neuronal model of induced-apoptosis. ⋯ In vitro studies showed that apoptotic rate was an independent factor associated with mortality at 6 months (p = 0.014). In the receiving operator curve (ROC) curve, a cut-off point of 66.5% showed a sensitivity of 89.5% and specificity of 66.7% in the prediction of patients' death. Cerebral apoptosis is a prominent form of cell death in the PCZ of human traumatic cerebral contusions, and high rates of in vitro apoptosis are associated with a poorer prognosis after TBI.