Journal of neurotrauma
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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.
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Journal of neurotrauma · Jan 2002
Axonal transection in adult rat brain induces transsynaptic apoptosis and persistent atrophy of target neurons.
We used the fimbria-fornix (FF) transection model of axonal injury to test the hypothesis that transneuronal degeneration occurs in the adult central nervous system in response to deafferentation. The medial mammillary nucleus, pars medialis (MMNm) was analyzed by light and electron microscopy at 3, 7, 14, and 30 days, and 6 months after unilateral FF transection in adult rat to identify the time course of neuronal responses in a remote target. Presynaptic terminals and neuronal cell bodies degenerated in the MMNm ipsilateral to FF transection. ⋯ The ultrastructure of this vacuolar degeneration was characterized by disorganization of the cytoplasm, formation of membrane-bound vacuolar cisternae and membranous inclusions, loss of organelles, cytoplasmic pallor, and chromatin alterations. This study shows that both anterograde axonal degeneration and transneuronal degeneration occur in a fornical target after FF axon transection. This transneuronal degeneration can be classified as sustained neuronal atrophy or transsynaptic apoptosis.
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Journal of neurotrauma · Dec 2001
Comparative StudyContrasting effects of dopamine therapy in experimental brain injury.
Management of cerebral perfusion pressure (CPP) is thought to be important for the treatment of traumatic brain injury (TBI). Vasopressors have been advocated as a method of increasing mean arterial blood pressure (mABP) and cerebral perfusion pressure (CPP) in the face of rising intracranial pressure (ICP). There are unresolved issues and theoretical risks about this therapy. ⋯ This occurred in the absence of ADCw changes, except in the contralateral hippocampus, where both water content and ADCw values rose with treatment, suggesting extracellular accumulation of water. In conclusion, although dopamine is capable of partially restoring CBF after injury, situations exist in which dopamine therapy worsens the swelling process. It is possible therefore that subgroups of patients exist who experience adverse effects of vasopressor treatment, and consequently the effects of vasopressor therapy in the clinical setting need to be more carefully evaluated.