Journal of neurotrauma
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Journal of neurotrauma · Jul 2008
Disruption of Bax protein prevents neuronal cell death but produces cognitive impairment in mice following traumatic brain injury.
Apoptosis contributes to delayed neuronal cell death in traumatic brain injury (TBI). To investigate if Bax plays a role in neuronal cell death and functional outcome after TBI, Bax gene disrupted (null) mice and wild-type (WT) controls were subjected to the controlled cortical impact (CCI) model of TBI. Motor function in WT and Bax null mice was evaluated using the round beam balance and the wire grip test on days 0-5. ⋯ At 24 h after trauma, Bax null mice had fewer TUNEL positive cells in the CA1 and dentate regions of hippocampus as compared to WT mice, suggesting that deletion of the Bax gene ameliorates hippocampal cell death after TBI. Sham-operated Bax null mice had significantly greater brain volume as compared to WT mice. Thus, it is possible that Bax deficiency in the transgenic mice produces developmental behavioral effects, perhaps due to Bax's role in regulating cell death during development.
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A three-dimensional (3D) finite element model (FEM) that simulates the Impactor weight-drop experimental model of traumatic spinal cord injury (SCI) was developed. The model consists of the rat spinal cord, with distinct element sets for the gray and white matter, the cerebrospinal fluid (CSF), the dura mater, a rigid rat spinal column, and a rigid impactor. Loading conditions were taken from the average impact velocities determined from previous parallel weight-drop experiments employing a 2.5-mm-diameter, 10-g rod dropped from either 12.5 or 25 mm. ⋯ The off-center impact had little effect on the rod trajectory, but caused marked shifts in the location of stress and strain contours. Different combinations of parameter values could reproduce the impactor trajectory, which suggests that another experimental measure of the tissue response is required for validation. The FEM can be a valuable tool for understanding the injury biomechanics associated with experimental SCI to identify areas for improvement in animal models and future research to identify thresholds for injury.
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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.