Journal of neurotrauma
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Journal of neurotrauma · Mar 2002
Randomized Controlled Trial Multicenter Study Clinical TrialHypothermia on admission in patients with severe brain injury.
Data from the "National Acute Brain Injury Study: Hypothermia" were examined to identify the impact of hypothermia on admission. In all patients, temperature was measured at randomization using bladder catheters with thermistors. Patients assigned to hypothermia were cooled using fluid-circulating pads. ⋯ Patients who were hypothermic on admission, age < or = 45 years (n = 81), and assigned to hypothermia had a significantly lower percentage of poor outcomes than those assigned to normothermia (hypothermia, 52%; normothermia, 76%; p = 0.02). Factors associated with hypothermia on admission were increased age, prehospital hypotension, smaller size, positive blood alcohol, larger volume of pre-hospital fluids, slightly higher injury severity, and winter enrollment The treatment effect was found in all of the four centers, which randomized the majority (80%) of the patients. It is unclear whether the improved outcome when hypothermia is maintained is a beneficial effect of very early hypothermia induction or an adverse effect of permitting the patients to rewarm passively.
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Journal of neurotrauma · Mar 2002
Acute ethanol intake attenuates inflammatory cytokines after brain injury in rats: a possible role for corticosterone.
It has been reported that acute ethanol intoxication exerts dose-dependent effects, both beneficial and detrimental, on the outcome of traumatic brain injury (TBI), although the mechanism(s) has not been determined. Given that pro-inflammatory cytokines are either neuroprotective or neurotoxic, depending on their tissue levels, ethanol-induced alterations in brain cytokine production may be involved in determining the recovery after TBI. The present study was undertaken to examine the effect of acute ethanol pretreatments (producing blood alcohol concentrations of 100+/-16 mg/dL, and 220+/-10 mg/dL, considered low and intoxicating doses, respectively) on interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) levels in discrete brain regions. ⋯ Ethanol pretreatment lowered cytokine levels in the cortex, hippocampus and hypothalamus in a dose-dependent manner after TBI compared to the untreated injured rats. Serum corticosterone levels were markedly increased in the injured rats, and were further augmented in the ethanol-pretreated injured animals in a dose-dependent manner. Our findings suggest that ethanol-induced decrease in pro-inflammatory cytokine production may be linked to increased circulating corticosterone, both of which may contribute to the outcome of brain injury.
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Journal of neurotrauma · Feb 2002
Development and characterization of a novel, graded model of clip compressive spinal cord injury in the mouse: Part 2. Quantitative neuroanatomical assessment and analysis of the relationships between axonal tracts, residual tissue, and locomotor recovery.
A detailed examination of the histopathological features of the clip compression injury in mice was performed to understand the relationships between neurological function and existing pathology of the spinal cord. Adult, female CD1 mice underwent three grades of extradural clip compression injury (3-g, 8-g, and 24-g FEJOTA mouse clips), transection, and sham injury at T3-4. Quantitative behavioural assessments were performed for 4 weeks following SCI. ⋯ The IP scores also correlated strongly with the persistence of extrapyramidal (raphespinal, reticulospinal, vestibulospinal and rubrospinal) tracts with correlation coefficients of 0.801, 0.782, 0.790, and 0.836, respectively (df = 28, p < 0.0001). These data indicate that the counts of retrogradely labeled neurons at the origin of distinct descending motor pathways are predictors of the variance of the functional recovery measured by the BBB and IP tests following spinal cord injury. In addition, we provide a detailed neuroanatomical study of clip compression injury in mice that can be used to study the molecular mechanisms of SCI in knockout and transgenic mice.
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Journal of neurotrauma · Feb 2002
Development and characterization of a novel, graded model of clip compressive spinal cord injury in the mouse: Part 1. Clip design, behavioral outcomes, and histopathology.
In order to take advantage of various genetically manipulated mice available to study the pathophysiology of spinal cord injury (SCI), we adapted an extradural clip compression injury model to the mouse (FEJOTA mouse clip). The dimensions of the modified aneurysm clip blades were customized for application to the mouse spinal cord. Three clips with different springs were made to produce differing magnitudes of closing force (3, 8, and 24 g). ⋯ Morphometric analyses of H&E/Luxol Fast Blue stained sections at every 50 microm from the injury epicenter indicated that with greater injury severity there was a progressive decrease in residual tissue (F = 220, df = 3; p < 0.0001; two-way ANOVA). In addition, statistically significant differences were found in the amount of residual tissue at the injury epicenter between all of the injury severities (p < 0.05, SNK test). This novel, graded compressive model of SCI will facilitate future studies of the pathological mechanisms of SCI using transgenic and knockout murine systems.
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Journal of neurotrauma · Jan 2002
Misclassification and treatment effect on primary outcome measures in clinical trials of severe neurotrauma.
The power of clinical trials depends mainly on the choice of the primary outcome measure, the statistical test, and the sample size. The most widely used outcome measure has been the five-category Glasgow Outcome Scale (GOS). Contrary to intuition, we show that more categories do not necessarily increase the power of a trial and actually can decrease power. ⋯ In the recently completed hypothermia trial, the use of a dichotomized GOS (good recovery/moderate disability versus severe disability/vegetative/dead) is shown to be more sensitive than use of three or more categories of the GOS. The results point to the importance of training study investigators who will collect the outcome data. The results also indicate that the number of categories should be carefully determined using the pilot data or the data from phase II trials.