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Item A Laser-Guided Spinal Cord Displacement Injury in Adult Mice(Mary Ann Liebert, 2019-02-01) Wu, Xiangbing; Qu, Wenrui; Bakare, Adewale A.; Zhang, Yi Ping; Fry, Collin M.E.; Shields, Lisa B.E.; Shields, Christopher B.; Xu, Xiao-Ming; Medicine, School of MedicineMouse models are unique for studying molecular mechanisms of neurotrauma because of the availability of various genetic modified mouse lines. For spinal cord injury (SCI) research, producing an accurate injury is essential, but it is challenging because of the small size of the mouse cord and the inconsistency of injury production. The Louisville Injury System Apparatus (LISA) impactor has been shown to produce precise contusive SCI in adult rats. Here, we examined whether the LISA impactor could be used to create accurate and graded contusive SCIs in mice. Adult C57BL/6 mice received a T10 laminectomy followed by 0.2, 0.5, and 0.8 mm displacement injuries, guided by a laser, from the dorsal surface of the spinal cord using the LISA impactor. Basso Mouse Scale (BMS), grid-walking, TreadScan, and Hargreaves analyses were performed for up to 6 weeks post-injury. All mice were euthanized at the 7th week, and the spinal cords were collected for histological analysis. Our results showed that the LISA impactor produced accurate and consistent contusive SCIs corresponding to mild, moderate, and severe injuries to the cord. The degree of injury severities could be readily determined by the BMS locomotor, grid-walking, and TreadScan gait assessments. The cutaneous hyperalgesia threshold was also significantly increased as the injury severity increased. The terminal lesion area and the spared white matter of the injury epicenter were strongly correlated with the injury severities. We conclude that the LISA device, guided by a laser, can produce reliable graded contusive SCIs in mice, resulting in severity-dependent behavioral and histopathological deficits.Item Sensorimotor Activity Partially Ameliorates Pain and Reduces Nociceptive Fiber Density in the Chronically Injured Spinal Cord(Mary Ann Liebert, 2018-09-15) Sliwinski, Christopher; Nees, Timo A.; Puttagunta, Radhika; Weidner, Norbert; Blesch, Armin; Neurological Surgery, School of MedicineA large proportion of patients suffering from spinal cord injury (SCI) develop chronic central neuropathic pain. Previously, we and others have shown that sensorimotor training early after SCI can prevent the development of mechanical allodynia. To determine whether training initiated in the subchronic/chronic phase remains effective, correlates of below-level neuropathic pain were analyzed in the hindpaws 5-10 weeks after a moderate T11 contusion SCI (50 kDyn) in adult female C57BL/6 mice. In a comparison of SCI and sham mice 5 weeks post-injury, about 80% of injured animals developed mechanical hypersensitivity to light mechanical stimuli, whereas testing of noxious stimuli revealed hypo-responsiveness. Thermal sensitivity testing showed a decreased response latency after injury. Without intervention, mechanical and thermal hyper-responsiveness were evident until the end of the experiment (10 weeks). In contrast, treadmill training (2 × 15 min/day; 5 × /week) initiated 6 weeks post-injury resulted in partial amelioration of pain behavior and this effect remained stable. Analysis of calcitonin gene-related peptide (CGRP)-labeled fibers in lamina III-IV of the lumbar dorsal horn revealed an increase in labeling density after SCI. This was not due to changes in the number or size distribution of CGRP-labeled lumbar dorsal root ganglion neurons. Treadmill training reduced the CGRP-labeling density in the spinal cord of injured mice, whereas the density of non-peptidergic isolectin-B4 (IB4)+ fibers showed no changes in lamina IIi and a slight reduction of sparse IB4 labeling in laminae III-IV. Thus, sensorimotor activity initiated in the subchronic/chronic phase of SCI remains effective in ameliorating pain behavior and influencing structural changes of the nociceptive system.Item A Tissue Displacement-based Contusive Spinal Cord Injury Model in Mice(JoVE, 2017-06-18) Wu, Xiangbing; Zhang, Yi Ping; Qu, Wenrui; Shields, Lisa B. E.; Shields, Christopher B.; Xu, Xiao-Ming; Neurological Surgery, School of MedicineProducing a consistent and reproducible contusive spinal cord injury (SCI) is critical to minimizing behavioral and histological variabilities between experimental animals. Several contusive SCI models have been developed to produce injuries using different mechanisms. The severity of the SCI is based on the height that a given weight is dropped, the injury force, or the spinal cord displacement. In the current study, we introduce a novel mouse contusive SCI device, the Louisville Injury System Apparatus (LISA) impactor, which can create a displacement-based SCI with high injury velocity and accuracy. This system utilizes laser distance sensors combined with advanced software to produce graded and highly-reproducible injuries. We performed a contusive SCI at the 10th thoracic vertebral (T10) level in mice to demonstrate the step-by-step procedure. The model can also be applied to the cervical and lumbar spinal levels.