In vitro model of neurotrauma using the chick embryo to test regenerative bioimplantation.

Effective repair of spinal cord injury sites remains a major clinical challenge. One promising strategy is the implantation of multifunctional bioscaffolds to enhance nerve fibre growth, guide regenerating tissue and modulate scarring/inflammation processes. Given their multifunctional nature, such implants require testing in models which replicate the complex neuropathological responses of spinal injury sites. This is often achieved using live, adult animal models of spinal injury. However, these have substantial drawbacks for developmental testing, including the requirement for large numbers of animals, costly infrastructure, high levels of expertise and complex ethical processes. As an alternative, we show that organotypic spinal cord slices can be derived from the E14 chick embryo and cultured with high viability for at least 24 days, with major neural cell types detected. A transecting injury could be reproducibly introduced into the slices and characteristic neuropathological responses similar to those in adult spinal cord injury observed at the lesion margin. This included aligned astrocyte morphologies and upregulation of glial fibrillary acidic protein in astrocytes, microglial infiltration into the injury cavity and limited nerve fibre outgrowth. Bioimplantation of a clinical grade scaffold biomaterial was able to modulate these responses, disrupting the astrocyte barrier, enhancing nerve fibre growth and supporting immune cell invasion. Chick embryos are inexpensive and simple, requiring facile methods to generate the neurotrauma model. Our data show the chick embryo spinal cord slice system could be a replacement spinal injury model for laboratories developing new tissue engineering solutions.

Utility of Magnetic Resonance Imaging for Ligamentous Injury in Cervical Spine Trauma: A 2-Year Consecutive Case Cohort.

BACKGROUND: Magnetic resonance imaging (MRI) is increasingly used as an adjunct to spinal soft tissue evaluation in cervical spine (C-spine) trauma; however, the utility of this information remains controversial. In this consecutive observational study, we reviewed the utility of MRI in patients with C-spine trauma. METHODS: We identified patients in real time over a 2-year period as they presented to our level 1 trauma center for C-spine computed tomography (CT) scan followed by MRI. MRI was obtained by the trauma team prior to the spine service consultation if (1) they were unable to clear the C-spine according to protocol or (2) if the on-call radiologist reported a concern for ligamentous integrity from the CT findings. RESULTS: Thirty-three patients, including 19 males (58%) and 14 females, with a mean age of 54 years, were referred to the spine service for concerns of ligamentous instability. The most common mechanisms of injury were motor vehicle accidents (n = 13) and falls (n = 11). MRI demonstrated ligamentous signal change identified by the radiologist as potentially unstable in all patients. Fifteen patients (45%) had multiple C-spine ligaments affected. The interspinous ligament was involved most frequently (28%), followed by the ligamentum flavum (21%) and supraspinous ligament (15%). All patients underwent dynamic upright C-spine X-rays that were interpreted by both the ordering surgeon and radiologist. There was no evidence of instability in any patient; concurrence between X-ray interpretation was 100%. The cervical collar was successfully removed in all cases. No patients required late surgical intervention, and there were no return visits to the emergency department of a spinal nature. CONCLUSIONS: MRI signal change within the ligaments of the C-spine should be interpreted with caution in the setting of trauma. To physicians less familiar with spinal biomechanics, MRI findings may be perceived in an inadvertently alarming manner. Bony alignment and, when indicated, dynamic upright X-rays remain the gold standard for evaluating the ligamentous integrity of the C-spine.

Dysphagia among geriatric trauma patients: A population-based study.

OBJECTIVE: To determine the significance of dysphagia on clinical outcomes of geriatric trauma patients. METHODS: This is a retrospective population-based study of geriatric trauma patients 65 years and older utilizing the Florida Agency for Health Care Administration dataset from 2010 to 2019. Patients with pre-admission dysphagia were excluded. Multivariable regression was used to create statistical adjustments. Primary outcomes included mortality and the development of dysphagia. Secondary outcomes included length of stay and complications. Subgroup analyses included patients with dementia, patients who received transgastric feeding tubes (GFTs) or tracheostomies, and speech language therapy consultation. RESULTS: A total of 52,946 geriatric patients developed dysphagia after admission during a 9-year period out of 1,150,438 geriatric trauma admissions. In general, patients who developed dysphagia had increased mortality, length of stay, and complications. When adjusted for traumatic brain and cervical spine injuries, the addition of mechanical ventilation decreased the mortality odds. This was also observed in the subset of patients with dysphagia who had GFTs placed. Of the three primary risk factors for dysphagia investigated, mechanical ventilation was the most strongly associated with later development of dysphagia and mortality. CONCLUSION: The geriatric trauma population is vulnerable to dysphagia with a large number associated with traumatic brain injury, cervical spine injury, and polytraumatic injuries that lead to mechanical ventilation. Earlier intubation/mechanical ventilation in association with GFTs was found to be associated with decreased inpatient hospital mortality. Tracheostomy placement was shown to be an independent risk factor for the development of dysphagia. The utilization of speech language therapy was found to be inconsistently utilized.

Early Intervention of Cold-Water Swimming on Functional Recovery and Spinal Pain Modulation Following Brachial Plexus Avulsion in Rats.

Brachial plexus avulsion (BPA) causes peripheral nerve injury complications with motor and sensory dysfunction of the upper limb. Growing evidence has shown an active role played by cold-water swimming (CWS) in alleviating peripheral neuropathic pain and functional recovery. This study examined whether CWS could promote functional recovery and pain modulation through the reduction of neuroinflammation and microglial overactivation in dorsal horn neurons at the early-stage of BPA. After BPA surgery was performed on rats, they were assigned to CWS or sham training for 5 min twice a day for two weeks. Functional behavioral responses were tested before and after BPA surgery, and each week during training. Results after the two-week training program showed significant improvements in BPA-induced motor and sensory loss (p < 0.05), lower inflammatory cell infiltration, and vacuole formation in injured nerves among the BPA-CWS group. Moreover, BPA significantly increased the expression of SP and IBA1 in dorsal horn neurons (p < 0.05), whereas CWS prevented their overexpression in the BPA-CWS group. The present findings evidenced beneficial rehabilitative effects of CWS on functional recovery and pain modulation at early-stage BPA. The beneficial effects are partially related to inflammatory suppression and spinal modulation. The synergistic role of CWS combined with other management approaches merits further investigation.

Bilateral facet effusion is a risk factor for segmental instability with cervical injury without vertebral fracture.

Magnetic resonance imaging (MRI) is effective in identifying cervical spine injury after trauma. However, cervical instability without major bone injury or dislocation is challenging to assess. Hence, the current study aimed to investigate and compare the MRI and radiography findings of segmental instability in patients with cervical spine injury. We investigated 34 participants with cervical spine injury without vertebral fracture. Based on the radiography findings, the participants were categorized into two: group A with segmental instability (n = 11) and group B without segmental instability (n = 23). Both groups were compared in terms of the presence of segmental instability on radiography and MRI. Anterior longitudinal ligament (ALL) injury, disc injury, and bilateral facet effusion were observed in 6/11, 5/11, and 7/11 patients in group A and in 5/23, 2/23 and 7/23 patients in group B, respectively. The results showed significant differences (p < 0.05). Moreover, 2 and 10 of 11 patients in group A and 16 and 7 of 23 patients in group B presented with hemi lateral facet effusion and paravertebral muscle injury, respectively. However, the results did not significantly differ. According to a logistic regression analysis, bilateral facet effusion after trauma was associated with cervical segmental instability (odd ratio: 10.6, 95% confidence interval: 1.31-84.7). Facet joint effusion might be caused by capsule injury during trauma. Most participants with segmental instability had ALL, disc, and flavum injury and bilateral facet effusion. Therefore, we need to consider bilateral facet effusion with other soft tissue damage of the cervical spine as an association factor to show the instability.

Life and Death in Italian Prehistory: The Case of the Sailor from Spina.

BACKGROUND: There are few reported cases in the literature of spinal injuries from the past, and all of them resulted in the death of the individual or led to severe health consequences. From the historical record, it is well known there were no cures or treatments for spinal lesions in the past. Given the paucity of historical documents focused on this topic, anthropological research on spinal injuries can contribute with important information regarding the medical history of this kind of trauma. Moreover, skeletal trauma and occupational markers may be crucial for the reconstruction of habitual behaviors and the identification of causes and timing of death. We report results of an anthropological study of a case of vertebral injury discovered in an individual from the Italian Iron Age that highlights this important topic. The aim of this study was to assess the habitual activity pattern and manner of death of an ancient inhabitant of Spina in Padanian Etruria (northeastern Italy). METHODS: We performed a detailed anthropological and paleopathological analysis of skeletal remains. RESULTS: The unknown individual was identified as a middle-aged man characterized by a particular trauma to the spine. Lesion analysis revealed a perimortem injury at the L2-L3 level. Characteristic markers on the bones indicated intense physical activity carried out during his life. CONCLUSIONS: This Etruscan, in all likelihood a sailor according to the occupational markers, did not survive a stabbing attack with a bladed weapon.

Gabapentinoid treatment promotes corticospinal plasticity and regeneration following murine spinal cord injury.

Axon regeneration failure causes neurological deficits and long-term disability after spinal cord injury (SCI). Here, we found that the α2δ2 subunit of voltage-gated calcium channels negatively regulates axon growth and regeneration of corticospinal neurons, the cells that originate the corticospinal tract. Increased α2δ2 expression in corticospinal neurons contributed to loss of corticospinal regrowth ability during postnatal development and after SCI. In contrast, α2δ2 pharmacological blockade through gabapentin administration promoted corticospinal structural plasticity and regeneration in adulthood. Using an optogenetic strategy combined with in vivo electrophysiological recording, we demonstrated that regenerating corticospinal axons functionally integrate into spinal circuits. Mice administered gabapentin recovered upper extremity function after cervical SCI. Importantly, such recovery relies on reorganization of the corticospinal pathway, as chemogenetic silencing of injured corticospinal neurons transiently abrogated recovery. Thus, targeting α2δ2 with a clinically relevant treatment strategy aids repair of motor circuits after SCI.

Evaluation of Rock Climbing Related Injuries in Older Athletes.

INTRODUCTION: With the growing enthusiasm from people of all ages about rock climbing and bouldering, adaptions and medical conditions of the older athlete have become increasingly important. We aimed to analyze injury demographics, distribution, and severity for the older rock-climbing athlete. METHODS: During a 3-y period, we performed a single-center injury surveillance in athletes ≥35 y of age presenting with rock climbing-related injuries or complaints. A standard questionnaire and examination protocol were conducted. RESULTS: A total of 198 patients (age 44.2±7.1 [35-77] y) (mean±SD, with range) with 275 independent injuries were recorded. Ninety percent of all injuries affected the upper extremity, 6% the lower extremity, and 4% other body regions. The Union Internationale des Associations d'Alpinisme injury scores were 2.0±0.3 (1-4), and no fatalities occurred. Acute injuries were observed in 32% and overuse injuries in 68% of all injuries. Among the overuse injuries, 47% were classified as degenerative overuse conditions. Athlete age did not significantly correlate with the development of overuse injuries and UIAA injury score, but subgroup analysis showed a weak correlation of the climber age with the development of degenerative conditions (P<0.05). The leading diagnosis of degenerative conditions was subacromial impingement syndrome of the shoulder. CONCLUSIONS: Compared to younger athletes, older rock climbers demonstrate a higher proportion of overuse injuries, especially degenerative conditions. Profound knowledge of climbing injuries patterns and conditions in older rock climbers is crucial to prevent injuries among all age groups and to decrease the number of degenerative injuries.

The distance of cervical vertebral dislocation could be a risk factor for blunt vertebral artery injury after traumatic cervical spine injury.

BACKGROUND: Blunt vertebral artery injury (BVAI) is a well-known potentially fatal complication of cervical spine injury. The condition is reported to be associated with vertebral fractures and cervical hyperextension. However, appropriate patient screening methods remain to be elucidated. This study aimed to identify the risk factors associated with BVAI in patients with cervical spine injury. METHODS: We conducted a retrospective, observational, single-centered study, including 137 patients with cervical spine injury transferred to our center from April 2007 to December 2016. Evaluation for BVAI was available in 62 patients based on magnetic resonance angiography or multi-detector computed tomography angiography. BVAI was classified using the Biffl grade. RESULTS: Among the 62 patients evaluated, 13 (21%) were diagnosed with BVAI. All injuries were classified as Biffl grade 2 (50%) or 4 (50%). Univariate analysis of patients with and without BVAI showed that cervical dislocation (p = 0.041) and low average hemoglobin level (p = 0.032) were associated with BVAI. On multivariate logistic regression analysis, cervical dislocation (odds ratio 1.189; 95% confidence interval 1.011-1.399, p = 0.036) remained a significant predictor of BVAI. Based on receiver operating characteristic (ROC) analysis, a dislocation > 6.7 mm was selected as the optimal cutoff value for prediction of BVAI (sensitivity and specificity, 87.5% and 71.4%, respectively). CONCLUSIONS: BVAI frequently occurred in combination with cervical spine dislocation, and the distance of the cervical dislocation was identified as a useful predictor of BVAI.

Imaging of cervical spine traumas.

Spinal traumas represent a significant proportion of muscle-skeletal injuries worldwide. Spinal injuries involve a complex structure with components having different traumatic susceptibility and variable healing capabilities. The interaction of numerous variables at time of trauma creates a great variety of lesions which makes challenging the creation and comparison of homogeneous groups, with difficulties in classifying spinal lesions, in assessing their instability, and in defining the indication and outcome of different treatment strategies. The evolution of concepts on instability has accompanied that of traumas classification schemes and treatment strategies. The assessment of instability in a spinal injury is actually crucial in front of newer surgical techniques and hardwares. Despite a long history of attempts to classify spinal traumas, it remains some degree of controversy in describing imaging data and a wide variety of treatment strategies. Acute cervical spine injuries affect from 1.9% to 4.6% of subjects reporting a blunt trauma, and up to 5.9% of multiple-injured patients. Most of spinal cord injuries are a consequence of unstable fractures of the cervical spine. An accurate and early diagnosis is mandatory to prevent neurological damage in unstable fractures. Classic and newer classifications are primarily based on features identifiable by using conventional imaging and CT scan, which are the most available modalities at most trauma centers. Even though multidetector-CT remains superior in assessing with high accuracy bone injuries, MRI is the most sensitive modality for detecting soft tissues injuries and spinal cord damage.

Non missile penetrating spinal injury.

Non-missile penetrating spinal injury (NMPSI) is a rare form of traumatic spinal injury. Cases with neurological deficit on presentation are treated surgically. In the extremely rare circumstance of NMPSI presenting with no neurological deficit the management is contentious. We report a case of a 43-year-old male presenting with a penetrating stab injury through the thoracolumbar spinal canal. On presentation he had no neurological deficits and subsequently the knife was removed in theatre without deep surgical exploration. In this report we review the literature of non-missile penetrating spinal injuries as well as their management and conclude that exploratory surgery for NMPSI without neurological deficit may not be necessary as previously thought.

AOSpine Subaxial Cervical Spine Injury Classification System: The Relationship Between Injury Morphology, Admission Injury Severity, and Long-Term Neurologic Outcome.

OBJECTIVE: The AOSpine Subaxial Cervical Spine Injury Classification System was introduced to improve communication, clinical management, and research. Here, the system was studied in relation to injury severity along with admission and long term neurologic follow-up. METHODS: A retrospective study was performed in subaxial cervical spine injury patients. Morphology was classified using the AOSpine Subaxial Cervical Spine Injury Classification System. Six major morphology subtypes were selected for analysis. The American Spinal Injury Association (ASIA) motor and Abbreviated Injury Severity (AIS) scores were recorded at admission and at follow-up >6 months. Admission intramedullary lesion length (IMLL) on MRI was recorded. RESULTS: In all, 82 patients met criteria for analysis. The mean follow-up time was 11 months (range, 6-33 months). The were 36 patients with morphology subtypes A0, 4 with A1/A2, 9 with A3/A4, 8 with B2, 11 with B3, and 14 with C. The A1/2 subtype had the least severe injuries on admission. The C and A3/A4 subtypes had the most severe injuries. The subtype C had the lowest ASIA Motor Score (AMS) and second highest percentage of complete injuries. A3/A4 patients had the highest percentage of complete injuries on admission. At follow-up, A3/A4 patients had the lowest AMS, and 33% of patients continued to have complete injuries. C subtype injuries all converted to AIS incomplete injuries on follow-up (P = 0.04). IMLL was found to be significantly different compared across multiple morphologic subtypes. Surgical management for each morphology subtype was reported. CONCLUSION: The AOSpine Subaxial Cervical Spine Injury Classification System successfully associated injury morphology with IMLL along with admission and long-term neurologic function and recovery.

Clinical Findings, Treatments and Outcomes in Farm Animals with Vertebral Fractures or Luxations: 22 Cases (2006-2017).

OBJECTIVE: The aim of this study was to describe the signalment, clinical presentation, diagnostic findings, medical and surgical treatment and outcome of 22 farm animals diagnosed with a vertebral fracture or luxation. STUDY DESIGN: Medical records of 22 farm animals (7 goats, 6 alpacas, 5 cattle, 3 sheep and 1 deer) were reviewed for signalment, history, presenting clinical signs and neurological examination findings, clinicopathological results, diagnostic imaging, final diagnosis, medical and surgical management, clinical progression and outcome. RESULTS: Animals' age ranged from 1 day to 15 years. Neurological examination findings included decreased motor function (20/22), recumbency (14/22), altered mentation (13/22), cranial nerve deficits (4/22) and lack of nociception (3/22). Lesions were localized to the atlanto-occipital region (2/22), C1 to C5 (7/22), C6 to T2 (4/22), T3 to L3 (3/22), and L4 to S1 (6/22). Diagnoses included vertebral fracture only (4/22), luxation only (5/22) or both vertebral fracture and luxation (13/22). In five cases, no therapy was attempted, while 12 cases were treated medically and five cases were treated surgically. Surgical interventions included manual reduction (n = 1); arthrodesis (n = 2); laminectomy (n = 1); and laminectomy with pin fixation, cerclage wire and polymethylmethacrylate bridging (n = 1). Five of the 22 cases survived to hospital discharge; two of these were treated surgically. CONCLUSION: The cervical region was most commonly affected. Prognosis for these injuries in farm animals is guarded.

Spinal injury analysis for typical snowboarding backward falls.

Spinal injury (SPI) often causes death and disability in snow-sport accidents. SPIs often result from spinal compression and flexion, but the injury risks due to over flexion have not been studied. Back protectors are used to prevent SPIs but the testing standards do not evaluate the flexion-extension resistance. To investigate SPI risks and to better define back-protector specifications, this study quantified the flexion-extension range of motions (ROMs) of the thoracic-lumbar spine during typical snowboarding backward falls. A human facet-multibody model, which was calibrated against spinal flexion-extension responses and validated against vehicle-pedestrian impact and snowboarding backward fall, was used to reproduce typical snowboarding backward falls considering various initial conditions (initial velocity, slope steepness, body posture, angle of approach, anthropometry, and snow stiffness). The SPI risks were quantified by normalizing the numerical spinal flexion-extension ROMs against the corresponding ROM thresholds from literature. A high risk of SPI was found in most of the 324 accident scenarios. The thoracic segment T6-T7 had the highest injury risk and incidence. The thoracic spine was found more vulnerable than the lumbar spine. Larger anthropometries and higher initial velocities tended to increase SPI risks while bigger angles of approach helped to reduce the risks. SPIs can result from excessive spinal flexion-extension during snowboarding backward falls. Additional evaluation of back protector's flexion-extension resistance should be included in current testing standards. An ideal back protector should consider the vulnerable spinal segments, the snowboarder's skill level and anthropometry.

Three-dimensional kinematic corridors of the head, spine, and pelvis for small female driver seat occupants in near- and far-side oblique frontal impacts.

OBJECTIVES: Analyses of recent automotive accident data indicate an increased risk of injury for small female occupants compared to males in similar accidents. Females have been shown to be more susceptible to spinal injuries than males. To protect this more vulnerable population, advanced anthropomorphic test devices (ATDs) and computer human body models are being developed and require biofidelity curves for validation. The aim of this study is to generate female-specific 3D kinematic corridors in near- and far-side oblique frontal impacts for the head, spine, and pelvis. METHODS: Eight specimens were procured and prescreened for mass, stature, and quantitative computed tomography bone mineral density and preexisting injuries to minimize biologic variability. Sets of 4 noncolinear retroreflective targets were placed on the back of the head; dorsal spine at T1, T8, and L2; and posterior sacrum. Instrumented computed tomography scans were obtained to measure the orientation and position of the markers relative to anatomic fiducials. The specimens were placed on a buck representative of a generic automotive driver's seat environment designed to minimize lower-extremity and pelvic motion. The buck was oriented such that the buck centerline was seated 30° from the impact vector in either a near- or far-side oblique frontal configuration. Preposition of the occupant was specified to the 50th percentile male H-point location, thigh and tibial angles, and torso angle. Impact was delivered via a servo-acceleration sled to the base of the buck with a 30 km/h 9 g trapezoidal pulse. Occupants were restrained by a standard 3-point belt that had a custom load-limiter device set to 2 kN at the D-ring side of the shoulder belt. Target motion was recorded at 1 kHz using a 3D optical motion capture system. Anatomic motion of the head, spine, and pelvis was calculated relative to the seat, and the average response was determined from 4 near-side and 4 far-side tests. The borders of the corridor were determined by calculating a standard deviational ellipse in the x, y, and z planes at each time step. RESULTS: Plots of the biofidelity corridors for near- and far-side tests are shown in planes parallel to the seat from the lateral, rear, and overhead directions. Averaged peak excursions in the fore/aft and lateral directions are compared for the near- and far-side corridors. Near-side female and male tests are similarly compared. CONCLUSIONS: In general, average peak excursions were greater in the far-side configuration than in the near-side configuration. Peak excursion results compared well with similar tests conducted on male postmortem human subjects (PMHS). The kinematic corridors developed in the current study serve as a set of biofidelity corridors for the development of current and future physical and computational surrogates.

The distribution of brachial plexus lesions after experimental traction: a cadaveric study.

OBJECTIVEThe objective of the present study was to determine experimentally the distribution of lesions caused in the cadaveric brachial plexus (BP) by excessive stretching. The authors attempted to delineate the correlation between the direction of stretching and sites of lesions.METHODSFifteen specimens (each comprised the spinal segment C4-T2 with 2 BPs) were harvested from adult cadavers. Each BP was stretched in a mechanical testing machine at a constant speed of 200 mm/min. Specimens were divided into 3 groups: in group A the BPs were stretched caudally at a 45° angle to the spinal midline; in group B they were stretched perpendicularly to the spinal midline; and in group C the stretching was caudally parallel to the midline. Lesions of each BP were identified and analyzed. A graph of load against dislocation was registered when stretching to delineate the maximal force (Fmax), defined as the maximum load at which BP failure occurs.RESULTSBased on macroscopic examination, 140 sites of mechanical damage were identified in 30 BPs. Preganglionic injuries (63.6% of lesions), defined as avulsions of the spinal ganglia with their rootlets, were found in 89 spinal nerves. In group B-in which specimens were stretched perpendicularly to the spinal segment-preganglionic injuries were significantly more frequent (41 avulsed spinal nerves) than in groups A and C (21 and 27 avulsed spinal nerves, respectively). Postganglionic lesions equivalent to neurotmesis were found in 51 sites (36.4% of all lesions) along spinal nerves, trunks, divisions, and cords. Postganglionic lesions in group B were much less frequent (8) as compared with groups A and C (24 and 19, respectively).CONCLUSIONSPredominance of preganglionic lesions suggests that attachments of the BP to the spine are more susceptible to traction than postganglionic elements. Preganglionic lesions were mainly produced in C7, C8, and T1 spinal nerves, suggesting their weaker attachment to the spine than in the case of C5 and C6 nerves. Preganglionic lesions were highly correlated with a traction perpendicular to the spine, whereas postganglionic lesions were provoked mainly by traction directed at 45° caudally or by means of caudal traction parallel to the midline. This discrepancy implies a relationship between mechanical resistance of pre- and postganglionic elements of the BP and the vector of force.

Ultrashortwave radiation promotes the recovery of spinal cord injury by inhibiting inflammation via suppression of the MK2/TNF­α pathway.

Mitogen­activated protein kinase­activated protein kinase 2 (MK2) and its mediated inflammation are involved in various diseases, including spinal cord injury (SCI). Ultrashortwave (USW) radiation has previously been reported to exert a protective effect on SCI. In the present study, through a series of reverse transcription­quantitative polymerase chain reaction (RT­qPCR), western blot and immunofluorescence assay, it was found that MK2 and tumor necrosis factor (TNF)­α/interleukin (IL)­1ß were elevated in patients with SCI and in H2O2­treated C8­D1A cells. Through gene level and protein level detection by using of RT­qPCR, western blot, immunofluorescence assay and terminal deoxynucleotidyl transferase (TdT) dUTP nick­end labeling assay, it was demonstrated that USW radiation inhibited the expression of MK2/TNF­α/IL­1ß and suppressed the apoptosis of H2O2­treated C8­D1A cells. Furthermore, it was confirmed that the overexpression of MK2 reversed the protective effect of USW on C8­D1A cells, which indicated that USW achieved its function via regulation of the MK2/TNF­α/IL­1ß pathway. Finally, using a constructed in vivo model and a series of RT­qPCR, western blot and IHC detection, it was confirmed that USW suppressed the expression of MK2 to promote functional recovery following SCI.

KLF6 and STAT3 co-occupy regulatory DNA and functionally synergize to promote axon growth in CNS neurons.

The failure of axon regeneration in the CNS limits recovery from damage and disease. Members of the KLF family of transcription factors can exert both positive and negative effects on axon regeneration, but the underlying mechanisms are unclear. Here we show that forced expression of KLF6 promotes axon regeneration by corticospinal tract neurons in the injured spinal cord. RNA sequencing identified 454 genes whose expression changed upon forced KLF6 expression in vitro, including sub-networks that were highly enriched for functions relevant to axon extension including cytoskeleton remodeling, lipid synthesis, and bioenergetics. In addition, promoter analysis predicted a functional interaction between KLF6 and a second transcription factor, STAT3, and genome-wide footprinting using ATAC-Seq data confirmed frequent co-occupancy. Co-expression of the two factors yielded a synergistic elevation of neurite growth in vitro. These data clarify the transcriptional control of axon growth and point the way toward novel interventions to promote CNS regeneration.

Effects of Level, Loading Rate, Injury and Repair on Biomechanical Response of Ovine Cervical Intervertebral Discs.

A need exists for pre-clinical large animal models of the spine to translate biomaterials capable of repairing intervertebral disc (IVD) defects. This study characterized the effects of cervical spinal level, loading rate, injury and repair with genipin-crosslinked fibrin (FibGen) on axial and torsional mechanics in an ovine cervical spine model. Cervical IVDs C2-C7 from nine animals were tested with cyclic tension-compression (- 240 to 100 N) and cyclic torsion (± 2° and ± 4°) tests at three rates (0.1, 1 and 2 Hz) in intact, injured and repaired conditions. Intact IVDs from upper cervical levels (C2-C4) had significantly higher torque range and torsional stiffness and significantly lower axial range of motion (ROM) and tensile compliance than IVDs from lower cervical levels (C5-C7). A tenfold increase in loading rate significantly increased torque range and torsional stiffness 4-8% (depending on amplitude) (p < 0.001). When normalized to intact, FibGen significantly restored torque range (FibGen: 0.96 ± 0.14, Injury: 0.88 ± 0.14, p = 0.03) and axial ROM (FibGen: 1.00 ± 0.05, Injury: 1.04 ± 0.15, p = 0.02) compared to Injury, with a values of 1 indicating full repair. Cervical spinal level must be considered for controlling biomechanical evaluations, and FibGen restored some torsional and axial biomechanical properties to intact levels.