A Laser-Guided Spinal Cord Displacement Injury in Adult Mice

Mouse 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

A Tissue Displacement-based Contusive Spinal Cord Injury Model in Mice

Producing 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

A Novel Vertebral Stabilization Method for Producing Contusive Spinal Cord Injury

Clinically-relevant animal cervical spinal cord injury (SCI) models are essential for developing and testing potential therapies; however, producing reliable cervical SCI is difficult due to lack of satisfactory methods of vertebral stabilization. The conventional method to stabilize the spine is to suspend the rostral and caudal cervical spine via clamps attached to cervical spinous processes. However, this method of stabilization fails to prevent tissue yielding during the contusion as the cervical spinal processes are too short to be effectively secured by the clamps (Figure 1). Here we introduce a new method to completely stabilize the cervical vertebra at the same level of the impact injury. This method effectively minimizes movement of the spinal column at the site of impact, which greatly improves the production of consistent SCIs. We provide visual description of the equipment (Figure 2-4), methods, and a step-by-step protocol for the stabilization of the cervical 5 vertebra (C5) of adult rats, to perform laminectomy (Figure 5) and produce a contusive SCI thereafter. Although we only demonstrate a cervical hemi-contusion using the NYU/MASCIS impactor device, this vertebral stabilization technique can be applied to other regions of the spinal cord, or be adapted to other SCI devices. Improving spinal cord exposure and fixation through vertebral stabilization may be valuable for producing consistent and reliable injuries to the spinal cord. This vertebral stabilization method can also be used for stereotactic injections of cells and tracers, and for imaging using two-photon microscopy in various neurobiological studies

Differences in Oxygen Uptake between Equivalent Resistance Training Protocols: Sets vs. Reps

We examined the energy costs of different resistance training protocols where exercise and recovery periods were equated: 48 total seconds of exercise and 210 seconds of between-set recovery. Two separate investigations were carried out at 65% of a 1 repetition maximum (1RM): back squat (7 men, 3 women) and bench press (9 men). Lifting cadence for concentric and eccentric phases was set at 1.5 sec each with 30 sec between-set recovery periods for the 8 sets, 2 reps protocol (sets) and a 3 min and 30 sec between-set recovery period for the 2 sets, 8 reps protocol (reps). The amount of oxygen consumed during lifting and between-set recovery periods was significantly greater for sets vs. reps protocol for both the back squat (+41%) and bench press (+27%) (p = 0.0001). Moreover, the total aerobic cost including the after-lifting excess post-exercise oxygen consumption (EPOC) was larger for the increased sets protocol for both the squat (+27%, p = 0.01) and bench press (+29%, p = 0.04). Total energy costs - aerobic plus anaerobic, exercise and recovery - were not different among sets or reps protocols. We conclude that a greater volume of oxygen is consumed with a lower repetition, increased number of sets resistance training protocol. We suggest that more recovery periods promote a greater potential for fat oxidation

Venipuncture-Related Median Nerve Palsy Disguised as Intraoperative Brachial Plexus Injury

Iatrogenic peripheral nerve injuries may result from transection, stretch, compression, injections, ligature, heat, anticoagulant use, and radiation. Iatrogenic median nerve palsy has been reported rarely. We report a case of a woman who underwent craniectomy for treatment of trigeminal neuralgia. Intraoperatively, a transient decline in the amplitude of the left upper extremity somatosensory evoked potentials (SSEPs) was noted. This finding was presumed to be due to the traction on the brachial plexus as it improved with repositioning. Immediately upon waking from anesthesia, the patient experienced sensorimotor deficits in the left median nerve distribution. Ecchymoses from venipuncture were observed in this area. Electrodiagnostic studies confirmed a left median nerve neuropathy localized in the antebrachial area. Neurosurgeons and neurologists should be alert to potential iatrogenic median nerve palsy following vascular access at the antebrachial region. Vascular access could be performed under the ultrasound guidance when a patient is under anesthesia or unable to give sensory feedback. Furthermore, placing an additional recording electrode over the proximal upper arm during intraoperative SSEP monitoring aids in distinguishing between brachial plexus and peripheral nerve injuries

Using Group Model Building to Understand Factors That Influence Childhood Obesity in an Urban Environment

Background: Despite increased attention, conventional views of obesity are based upon individual behaviors, and children and parents living with obesity are assumed to be the primary problem solvers. Instead of focusing exclusively on individual reduction behaviors for childhood obesity, greater focus should be placed on better understanding existing community systems and their effects on obesity. The Milwaukee Childhood Obesity Prevention Project is a community-based coalition established to develop policy and environmental change strategies to impact childhood obesity in Milwaukee, Wisconsin. The coalition conducted a Group Model Building exercise to better understand root causes of childhood obesity in its community. Methods: Group Model Building is a process by which a group systematically engages in model construction to better understand the systems that are in place. It helps participants make their mental models explicit through a careful and consistent process to test assumptions. This process has 3 main components: (1) assembling a team of participants; (2) conducting a behavior-over-time graphs exercise; and (3) drawing the causal loop diagram exercise. Results: The behavior-over-time graph portion produced 61 graphs in 10 categories. The causal loop diagram yielded 5 major themes and 7 subthemes. Conclusions: Factors that influence childhood obesity are varied, and it is important to recognize that no single solution exists. The perspectives from this exercise provided a means to create a process for dialogue and commitment by stakeholders and partnerships to build capacity for change within the community

Transplantation of Ciliary Neurotrophic Factor-Expressing Adult Oligodendrocyte Precursor Cells Promotes Remyelination and Functional Recovery after SpinalCord Injury

Demyelination contributes to the dysfunction after traumatic spinal cord injury (SCI). We explored whether the combination of neurotrophic factors and transplantation of adult rat spinal cord oligodendrocyte precursor cells (OPCs) could enhance remyelination and functional recovery after SCI. Ciliary neurotrophic factor (CNTF) was the most effective neurotrophic factor to promote oligodendrocyte (OL) differentiation and survival of OPCs in vitro. OPCs were infected with retroviruses expressing enhanced green fluorescent protein (EGFP) or CNTF and transplanted into the contused adult thoracic spinal cord 9 d after injury. Seven weeks after transplantation, the grafted OPCs survived and integrated into the injured spinal cord. The survival of grafted CNTF-OPCs increased fourfold compared with EGFP-OPCs. The grafted OPCs differentiated into adenomatus polyposis coli (APC+) OLs, and CNTF significantly increased the percentage of APC+ OLs from grafted OPCs. Immunofluorescent and immunoelectron microscopic analyses showed that the grafted OPCs formed central myelin sheaths around the axons in the injured spinal cord. The number of OL-remyelinated axons in ventrolateral funiculus (VLF) or lateral funiculus (LF) at the injured epicenter was significantly increased in animals that received CNTF-OPC grafts compared with all other groups. Importantly, 75% of rats receiving CNTF-OPC grafts recovered transcranial magnetic motor-evoked potential and magnetic interenlargement reflex responses, indicating that conduction through the demyelinated axons in VLF or LF, respectively, was partially restored. More importantly, recovery of hindlimb locomotor function was significantly enhanced in animals receiving grafts of CNTF-OPCs. Thus, combined treatment with OPC grafts expressing CNTF can enhance remyelination and facilitate functional recovery after traumatic SCI

An In Vivo Duo-color Method for Imaging Vascular Dynamics Following Contusive Spinal Cord Injury

Spinal cord injury (SCI) causes significant vascular disruption at the site of injury. Vascular pathology occurs immediately after SCI and continues throughout the acute injury phase. In fact, endothelial cells appear to be the first to die after a contusive SCI. The early vascular events, including increased permeability of the blood-spinal cord barrier (BSCB), induce vasogenic edema and contribute to detrimental secondary injury events caused by complex injury mechanisms. Targeting the vascular disruption, therefore, could be a key strategy to reduce secondary injury cascades that contribute to histological and functional impairments after SCI. Previous studies were mostly performed on postmortem samples and were unable to capture the dynamic changes of the vascular network. In this study, we have developed an in vivo duo-color two-photon imaging method to monitor acute vascular dynamic changes following contusive SCI. This approach allows detecting blood flow, vessel diameter, and other vascular pathologies at various sites of the same rat pre- and post-injury. Overall, this method provides an excellent venue for investigating vascular dynamics

The Chandra XBootes Survey - III: Optical and Near-IR Counterparts

The XBootes Survey is a 5-ks Chandra survey of the Bootes Field of the NOAO Deep Wide-Field Survey (NDWFS). This survey is unique in that it is the largest (9.3 deg^2), contiguous region imaged in X-ray with complementary deep optical and near-IR observations. We present a catalog of the optical counterparts to the 3,213 X-ray point sources detected in the XBootes survey. Using a Bayesian identification scheme, we successfully identified optical counterparts for 98% of the X-ray point sources. The optical colors suggest that the optically detected galaxies are a combination of z<1 massive early-type galaxies and bluer star-forming galaxies whose optical AGN emission is faint or obscured, whereas the majority of the optically detected point sources are likely quasars over a large redshift range. Our large area, X-ray bright, optically deep survey enables us to select a large sub-sample of sources (773) with high X-ray to optical flux ratios (f_x/f_o>10). These objects are likely high redshift and/or dust obscured AGN. These sources have generally harder X-ray spectra than sources with 0.1<f_x/f_o<10. Of the 73 X-ray sources with no optical counterpart in the NDWFS catalog, 47 are truly optically blank down to R~25.5 (the average 50% completeness limit of the NDWFS R-band catalogs). These sources are also likely to be high redshift and/or dust obscured AGN.Comment: 19 pages, 13 figures, ApJ accepted. Catalog can be found at: http://www.noao.edu/noao/noaodeep or ftp://archive.noao.edu/pub/catalogs/xbootes

Descending motor circuitry required for NT-3 mediated locomotor recovery after spinal cord injury in mice

Locomotor function, mediated by lumbar neural circuitry, is modulated by descending spinal pathways. Spinal cord injury (SCI) interrupts descending projections and denervates lumbar motor neurons (MNs). We previously reported that retrogradely transported neurotrophin-3 (NT-3) to lumbar MNs attenuated SCI-induced lumbar MN dendritic atrophy and enabled functional recovery after a rostral thoracic contusion. Here we functionally dissected the role of descending neural pathways in response to NT-3-mediated recovery after a T9 contusive SCI in mice. We find that residual projections to lumbar MNs are required to produce leg movements after SCI. Next, we show that the spared descending propriospinal pathway, rather than other pathways (including the corticospinal, rubrospinal, serotonergic, and dopaminergic pathways), accounts for NT-3-enhanced recovery. Lastly, we show that NT-3 induced propriospino-MN circuit reorganization after the T9 contusion via promotion of dendritic regrowth rather than prevention of dendritic atrophy