Journal of neurotrauma
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Journal of neurotrauma · Aug 2008
Effect of cervical dorsolateral funiculotomy on reach-to-grasp function in the rat.
Cervical spinal cord injury (SCI) can severely impair reaching and grasping ability, and several descending systems, including the rubrospinal tract and corticospinal tract, have been implicated in the control of reach-to-grasp movements. The primary aim of this study was to characterize further the forelimb deficits associated with a cervical dorsolateral funiculotomy, which ablates the rubrospinal tract but spares the dorsal and ventral corticospinal tract in the rat. Adult female rats that preferred to use their right forelimb to reach for single pellets received a lesion to the right cervical dorsolateral funiculus between the C3-4 dorsal roots. ⋯ Quantitative kinematics also revealed a reduction in digit abduction during the reach, which persisted throughout the 8-week post-SCI period. Tests of reach-to-grasp function, therefore, were more sensitive than a test of gross forelimb usage after cervical dorsolateral funiculotomy and did not show recovery over the 8-week survival period. We suggest that the staircase test is a useful screening tool for intervention studies because of its ease of implementation, and that the single pellet test is valuable for examining reaching accuracy and detailed kinematics.
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Journal of neurotrauma · Jul 2008
Agrin expression during synaptogenesis induced by traumatic brain injury.
Interaction between extracellular matrix proteins and regulatory proteinases can mediate synaptic integrity. Previously, we documented that matrix metalloproteinase 3 (MMP-3) expression and activity increase following traumatic brain injury (TBI). We now report protein and mRNA analysis of agrin, a MMP-3 substrate, over the time course of trauma-induced synaptogenesis. ⋯ By contrast, MK-801 in the combined insult failed to significantly change 7-day agrin transcript, mRNA levels remaining elevated over uninjured sham cases. Together, these results suggest that agrin plays an important role in the sprouting phase of reactive synaptogenesis, and that both its expression and distribution are correlated with extent of successful recovery after TBI. Further, when pathogenic conditions which induce synaptic plasticity are reduced, increase in agrin mRNA is attenuated.
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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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The heterogeneity of traumatic brain injury (TBI) is considered one of the most significant barriers to finding effective therapeutic interventions. In October, 2007, the National Institute of Neurological Disorders and Stroke, with support from the Brain Injury Association of America, the Defense and Veterans Brain Injury Center, and the National Institute of Disability and Rehabilitation Research, convened a workshop to outline the steps needed to develop a reliable, efficient and valid classification system for TBI that could be used to link specific patterns of brain and neurovascular injury with appropriate therapeutic interventions. Currently, the Glasgow Coma Scale (GCS) is the primary selection criterion for inclusion in most TBI clinical trials. ⋯ Outcome assessment would utilize endpoints relevant to the targeted injury type. Advantages and disadvantages of currently available diagnostic, monitoring, and assessment tools were discussed. Recommendations were made for enhancing the utility of available or emerging tools in order to facilitate implementation of a pathoanatomic classification approach for clinical trials.