Spinal Sites Research Articles

The Association of Coronary Artery Calcium Score and Osteoporosis in Postmenopausal Women: A Cross-Sectional Study.

The association between osteoporosis, a common metabolic bone disorder, and atherosclerosis has been reported in different studies. In this study, we aimed to investigate the association between the coronary artery calcium score (CACS) and bone mineral density (BMD) at different sites and bone biomarkers in postmenopausal women. A total of 184 participants were enrolled in this study. The CACS and BMD at different sites, including the spinal, total hip, and femoral neck, were measured using computed tomography angiography and dual energy X-ray absorptiometry, respectively. Serum levels of osteocalcin, β-C-terminal telopeptide (β-CTX), parathyroid hormone, and 25-hydroxy-vitamin D were measured. A negative association between CACS and bone biomarker levels (osteocalcin, P=0.021; β-CTX, P=0.013) was noted. The univariable model showed an association between CACS and osteoporosis of the femoral neck (P=0.03). It was found that with an increase of 10 U in CACS, the odds of osteoporosis at the femoral neck escalates by 2% (odds ratio=1.02, 95% confidence interval, 1.002-1.03) using the multivariate logistic regression model, while such an association with osteoporosis could not be found at the spinal site. The best cutoff point of the calcium score was estimated to be 127. The results suggest that in postmenopausal women, coronary atherosclerosis is independently associated with osteoporosis of the femoral neck, but such an association could not be detected with spinal osteoporosis. The importance of screening for osteoporosis in patients with cardiovascular disease and the implications of preventive measures in the primary care setting were highlighted considering the common risk factors.

Use of specific agar plates for early detection of anaerobic bacteria in surgical site infections after spinal surgery: a prospective single centre study.

To determine if additional agar plates could allow earlier detection of anaerobes in spinal surgical site infections (SSIs), we performed a prospective study (November 2017-January 2019) of patients with early spinal SSIs. In addition to routine 14-day cultures, surgical samples were inoculated onto three additional plates (CDC anaerobe agar with 5% sheep blood [CDC], CDC anaerobe laked sheep blood agar with kanamycin/vancomycin [BBL], and Bacteroides bile esculin [BBE] agar with amikacin (BD, USA)) incubated under anaerobic conditions (72 h, 37°C). The primary endpoint was detection of anaerobes by these methods, as compared to routine culture. Anaerobes were identified in 7/61 patients (11%) using the routine procedure and in one extra case with additional plates (overall detection rate 8/61, 13%). Sensitivity was greater for the CDC plate than for the BBL and BBE plates. When routine culture was positive, the CDC plate was always positive, and in three cases showed at least one additional anaerobe. Using additional agar plates, anaerobes were identified in early spinal SSI in 13% of patients. Within 3 days, CDC agar plate enabled detection of anaerobes in one extra case and at least one additional anaerobe in three other cases, compared to routine 14-day culture.

GelMA-MXene hydrogel nerve conduits with microgrooves for spinal cord injury repair

Repair of spinal cord injury (SCI) depends on microenvironment improvement and the reconnection between injured axons and regenerated neurons. Here, we fabricate a GelMA-MXene hydrogel nerve conduit with electrical conductivity and internal-facing longitudinal grooves and explore its function in SCI repair. It is found that the resultant grooved GelMA-MXene hydrogel could effectively promote the neural stem cells (NSCs) adhesion, directed proliferation and differentiation in vitro. Additionally, when the GelMA-MXene conduit loaded with NSCs (GMN) is implanted into the injured spinal cord site, effective repair capability for the complete transection of SCI was demonstrated. The GMN group shows remarkable nerve recovery and significantly higher BBB scores in comparison to the other groups. Therefore, GMN with the microgroove structure and loaded with NSCs is a promising strategy in treating SCI.

Safety and Efficacy of Dose-Escalated Radiation Therapy With a Simultaneous Integrated Boost for the Treatment of Spinal Metastases

PurposeIntensity modulated radiation therapy (RT) for spine metastases using a simultaneous integrated boost (SSIB) was shown as an alternative to the treatment of select osseous metastases that are not amenable to spine stereotactic radiosurgery. We sought to update our clinical experience using SSIB in patients for whom dose escalation was warranted but spine stereotactic radiosurgery was not feasible. Methods and MaterialsA total of 58 patients with 63 spinal metastatic sites treated with SSIB between 2012 and 2021 were retrospectively reviewed. The gross tumor volume and clinical target volume were prescribed 40 and 30 Gy in 10 fractions, respectively. ResultsThe median follow-up time was 31 months. Of 79% of patients who reported pain before RT with SSIB, 82% reported an improvement following treatment. Patient-reported pain scores on a 10-point scale revealed a significant decrease in pain at 1, 3, 6, and 12 months after SSIB (P < .0001). Additionally, there were limited toxicities; only 1 patient suffered grade 3 toxicity (pain) following RT. There were no reports of radiation-induced myelopathy at last follow-up, and 8 patients (13%) experienced a vertebral column fracture post-treatment. Local control was 88% (95% confidence interval [CI], 80%-98%) and 74% (95% CI, 59%-91%) at 1 and 2 years, respectively. Overall survival was 64% (95% CI, 53%-78%) and 45% (95% CI, 34%-61%) at 1 and 2 years, respectively. The median overall survival was 18 months (95% CI, 13-27 months). Multivariable analysis using patient, tumor, and dosimetric characteristics revealed that a higher Karnofsky performance status before RT (hazard ratio, 0.44, 0.22-0.89; P = .02) was associated with longer survival. ConclusionsThese data demonstrate excellent pain relief and local control with limited acute toxicities following treatment with RT using SSIB to 40 Gy. Collectively, our data suggest that dose escalation to spine metastases using SSIB can be safe and efficacious for patients, especially those with radioresistant disease. Further investigation is warranted to validate these findings.

Intrathecal minocycline does not block the adverse effects of repeated, intravenous morphine administration on recovery of function after SCI

Opioids are among the most effective analgesics for the management of pain in the acute phase of a spinal cord injury (SCI), and approximately 80% of patients are treated with morphine in the first 24 h following SCI. We have found that morphine treatment in the first 7 days after SCI increases symptoms of pain at 42 days post-injury and undermines the recovery of locomotor function in a rodent model. Prior research has implicated microglia/macrophages in opioid-induced hyperalgesia and the development of neuropathic pain. We hypothesized that glial activation may also underlie the development of morphine-induced pain and cell death after SCI. Supporting this hypothesis, our previous studies found that intrathecal and intravenous morphine increase the number of activated microglia and macrophages present at the spinal lesion site, and that the adverse effects of intrathecal morphine can be blocked with intrathecal minocycline. Recognizing that the cellular expression of opioid receptors, and the intracellular signaling pathways engaged, can change with repeated administration of opioids, the current study tested whether minocycline was also protective with repeated intravenous morphine administration, more closely simulating clinical treatment. Using a rat model of SCI, we co-administered intravenous morphine and intrathecal minocycline for the first 7 days post injury and monitored sensory and locomotor recovery. Contrary to our hypothesis and previous findings with intrathecal morphine, we found that minocycline did not prevent the negative effects of morphine. Surprisingly, we also found that intrathecal minocycline alone is detrimental for locomotor recovery after SCI. Using ex vivo cell cultures, we investigated how minocycline and morphine altered microglia/macrophage function. Commensurate with published studies, we found that minocycline blocked the effects of morphine on the release of pro-inflammatory cytokines but, like morphine, it increased glial phagocytosis. While phagocytosis is critical for the removal of cellular and extracellular debris at the spinal injury site, increased phagocytosis after injury has been linked to the clearance of stressed but viable neurons and protracted inflammation. In sum, our data suggest that both morphine and minocycline alter the acute immune response, and reduce locomotor recovery after SCI.

Safety and Efficacy of Dose-Escalated Radiotherapy with a Simultaneous Integrated Boost for the Treatment of Spinal Metastases

<h3>Purpose/Objective(s)</h3> Dose-escalated radiotherapy (RT) using a spinal simultaneous integrated boost (SSIB) has been recently utilized for treatment of metastatic lesions not amenable to spine stereotactic radiosurgery (SSRS). Prior reports have utilized small sample sizes with short follow-up times. Our goal was to characterize the long-term efficacy and safety of this technique in a large cohort of patients with long term follow-up. <h3>Materials/Methods</h3> We reviewed 58 patients with 63 spinal metastatic sites that were treated with RT using a SSIB between 2012 and 2021. All patients received 30 Gy to the clinical tumor volume (CTV)and 40 Gy to the gross tumor volume, each delivered simultaneously in 10 fractions (GTV). Acute and late toxicities were noted for each patient. Local control (LC) was defined as having no progression on magnetic resonance imaging (MRI) at the SSIB-treated site. Overall survival (OS) was defined as the time from initiation of SSIB to death or last follow up, and was estimated using the Kaplan-Meier method. Multivariable Cox analysis was performed to identify associations with OS and LC. <h3>Results</h3> In our cohort, the median Karnofsky Performance Score (KPS) prior to RT was 80 (interquartile range [IQR], 80-90). Tumor histology was considered to be radioresistant in 81% of patients. Most patients had paraspinal involvement (65%) and epidural extension (82%). The median follow-up was 31 months with a median OS of 18 months (95% confidence interval [CI], 13-27 months). OS at 1, 2, and 3 years were 64%, 45%, and 24%, respectively. Actuarial LC was 98% (CI, 95-100%) and 95% (CI, 89-100%) at 1 and 2 years, respectively. The median GTV and CTV doses were 4123 cGy (range, 3400-4318 cGy) and 3641 cGy (range, 3302-4089 cGy), respectively. The mean cord dose was 2401 cGy (range 59-3168 cGy). The most commonly observed acute toxicities were fatigue (41%), pain (38%), esophagitis (8%), and nausea (8%). However, only one patient (2%) experienced Grade 3 or higher toxicity (pain). At last follow-up, no patients had developed myelopathy and all patients maintained ambulation. Following RT, pain improvement was achieved in 82% with a median pain score of 2 (IQR, 1-4) out of 10 from a pre-RT baseline of 4 (IQR, 3-6). Multivariable Cox analysis revealed that higher KPS score prior to RT (hazard ratio [HR], 0.40, 95%, CI, 0.20-0.84; <i>P</i>=0.016) was associated with longer OS, whereas increased size of PTV (HR 1.003, CI 1.001-1.005; <i>P</i>=0.017) was associated with shorter survival. <h3>Conclusion</h3> Our data show that the use of RT with SSIB provides favorable LC and OS with improved pain relief for selected patients that are not amenable for SSRS. Importantly, there were limited acute toxicities with no observed instances of radiation-induced myelopathy. Multi-institutional validation is warranted.

Research on Polycaprolactone-Gelatin Composite Scaffolds Carrying Nerve Growth Factor for the Repair of Spinal Cord Injury.

Objective This study was to investigate the mechanism of action of polycaprolactone/gelatin (PCL/GE) composite fiber scaffold with nerve growth factor (NGF) in the recovery of spinal cord injury (SCI). Methods Sixty female Sprague-Dawley (SD) rats were randomly assigned to the negative control group, the positive control group, the PCL/GE scaffold group, and the collagen-binding structural domain nerve growth factor (CBD-NGF)/PCL/GE scaffold group, with 15 rats in each group. Spinal cord transection was used to establish SCI models in rats. The negative control group received sham surgery, while the other three groups were given spinal cord transection at the tenth thoracic vertebra (T10) segment. The rats in the PCL/GE scaffold group were implanted with a 4 mm PCL/GE composite fiber scaffold, and those in the CBD-NGF/PCL/GE scaffold group were implanted with a CBD-NGF/PCL/GE composite fiber scaffold. The Basso–Beattie–Bresnahan (BBB) locomotor rating scale was used to evaluate the locomotor ability of the hind limbs of the rats, and the amplitude and latency of motor evoked potentials (MEP) were recorded by neurophysiological testing at 12 w postoperatively. The levels of growth-associated protein 43 (GAP43) and neurofilament protein 200 (NF200) in the spinal cord tissue of the injury site were determined using Western Blot at 12 w after surgery. Spinal cord tissues of 2 cm within the injury site, the thoracic segment above the injury site, and the lumbar segment below the injury site were collected from the measurement of axonal transport using fluorescent retrograde tracer fluorogold, and the integrated absorbance (IA) values of FC-positive cells were calculated. Results After treatment, the negative control rats showed normal locomotion function of the hind limb with the highest BBB scores, while the positive control rats had the lowest BBB scores and showed paraplegia. The scaffold groups exhibited better locomotion function of the hind limb and higher BBB scores than the positive controls, with greater improvement observed in the CBD-NGF/PCL/GE scaffold group (P < 0.05). Compared with the positive controls, the PCL/GE scaffold group and CBD-NGF/PCL/GE scaffold group exhibited significantly shorter latency and increased amplitude of MEP, with more significant changes observed in the CBD-NGF/PCL/GE scaffold group (P < 0.05). Compared with the positive control group, the GAP43 and NF200 levels of spinal cord tissue were significantly elevated in both the PCL/GE scaffold group and the CBD-NGF/PCL/GE scaffold group, and the changes were more pronounced in the CBD-NGF/PCL/GE scaffold group (P < 0.05). The differences in the IA values of FC-positive cells in the spinal cord tissue of the lumbar segment below the injury site among the four groups did not come up to the statistical standard (P > 0.05). Compared with the positive control group, the FC-positive cell IA values of spinal cord tissue in the thoracic segment above the injury area were markedly increased in the PCL/GE scaffold group and the CBD-NGF/PCL/GE scaffold group, and the alterations were more significant in the CBD-NGF/PCL/GE scaffold group (P < 0.05). Conclusion PCL/GE composite fiber scaffold with NGF significantly improves motor and neurological functions in the hind limbs of SCI rats and promotes the recovery of axonal transport, and the mechanism may be associated with the upregulation of GAP43 and NF200 levels in spinal cord injury site tissues.

Safety and effectiveness of fondaparinux as a postpartum thromboprophylaxis during puerperium among muslim women: A single centre prospective study.

Background: Venous thromboembolism (VTE) remains one of the leading causes of maternal morbidity and mortality, with postpartum period carrying the greatest risk. Perinatal thromboprophylaxis is often administered based on risk-factor assessment. Low molecular weight heparin has a proven safety profile in the obstetrics population, however, its porcine-derived content may lead to reduced uptake amongst certain religious groups. We aimed to evaluate the safety of fondaparinux as an alternative postpartum thromboprophylaxis. Methods: We conducted a prospective, single arm, open label study from September 2017 until March 2018. Women who fulfilled the criteria for post natal thromboprophylaxis based on the 2015 RCOG guidelines were recruited. Each patient received subcutaneous injection of Fondaparinux, 2.5 mg daily for 10 days. A telephone interview was conducted on day 10 post delivery. Each woman was subsequently reviewed in the outpatient clinic 6 weeks postpartum. The primary outcome measure was occurrence of pulmonary embolism or deep vein thrombosis suggestive by clinical symptoms and assessment. Secondary outcome measures were allergic reaction and bleeding tendency such as secondary post-partum haemorrhage, spinal site bleeding and wound haematoma. Allergic reaction and bleeding tendency in neonates were also recorded. Results: Sixty women were included in the analysis. There were no VTE cases amongst our cohort. No major bleeding was recorded. Two patients (3.3%) had wound haematoma, one of which occurred 3 weeks post delivery. No adverse effect in neonates was noted. Conclusion: Fondaparinux is a safe alternative thromboprophylaxis for postpartum women.

Pharmacological inhibition of DKK1 promotes spine fusion in an ovariectomized rat model.

Osteoporosis is common in patients undergoing spine surgery, and carries a considerable risk of adverse outcomes. New methods to positively influence bone regeneration and spine fusion under osteoporotic conditions would be impactful. Neutralizing anti-Dickkopf-1 (DKK1) antibodies has been used as a bone anabolic agent, and recently reported by our group to aid in stem cell-mediated appendicular bone regeneration. Here, a small molecule designed as a DKK1 inhibitor, WAY-262611, was used to induce posterolateral spine fusion in an ovariectomized rat model. In vitro, pharmacological inhibition of DKK1 enhanced osteogenesis and Wnt signaling activity among rat bone marrow-derived stem/stromal cells (BMSCs). In vivo, systemic treatment with WAY-262611 promoted both chondrogenesis and osteogenesis within the spinal fusion site, and ultimately led to significant improvements in lumbar fusion as assessed by XR, μCT, histology and manual palpation assessments. No significant effect on osteoclast numbers or fusion site angiogenesis was detected, suggesting a primary direct effect on mesenchymal cells of the implantation site. Finally, evidence from human stem/stromal cells further demonstrated that pharmacologic inhibition of DKK1 promoted osteogenic differentiation in vitro. Taken together, our results suggest that targeting DKK1 promotes local bone formation and suggests potential clinical value for osteoporotic bone repair.

Follow-up MRI appearance of the surgical site in dogs treated for thoracolumbar intervertebral disc herniation and showing ongoing or recurrent neurological symptoms.

Reherniation and reoperation rates of 4.5%-36% are reported in canine patients treated for intervertebral disc herniation (IVDH). Decision-making for surgical reintervention can prove challenging, especially since common postoperative changes are poorly described on MRI. The purpose of this single-center, retrospective, descriptive study was to describe the MRI characteristics ofthe surgical site in dogs treated for thoracolumbar IVDH and presenting for ongoing or recurrent neurological signs. Twenty-one patients were included for a total of 42 MRI studies. Chondrodystrophic breeds, specifically Dachshunds, were overrepresented. Mean number of days between surgery and second MRI was335(range 2-1367). Metallic susceptibility artifacts were seen in seven of 21cases(33%), but these were limited in extent, spanning on average 1.3 vertebral bodies. In 11 cases, spinal cord compression suspected to be clinically significant was found at the surgical site; the extradural compressive material consisted of intervertebral disc material only, or a combination of intervertebral disc material and hematoma or inflammatory changes in 10 cases, and a displaced articular process and fibrous tissue in one case. The latter is a newly described complication of mini-hemilaminectomies. Paravertebral soft tissue changes and vertebral new bone formation varied according to the postoperative stage at which the patients were imaged. The results of this study supported the use of MRI as a diagnostic modality for spinal imaging following IVDH surgery, and showed that the presence of extradural disc material at a spinal surgical site is common along with various vertebral and paravertebral changes.

More Attention on Segments Remote from the Primary Spinal Cord Lesion Site.

Recent findings from multimodal imaging studies point to macrostructural pathological changes in areas significantly distant from the epicenter of spinal cord injury, both in the spinal cord and in the brain. Studies are being performed to determine cellular and molecular mechanisms of these shifts, which are currently poorly understood. Research has demonstrated that the pathological process in the remote area is multifaceted. This process involves astrocytes and microglia, which contribute to the degeneration of nerve fibers passing from and through the immediate impact area, as well as participate in reciprocal activation. As a result, there is accompanying synaptic loss in areas remote to the spinal cord injury location. Reactive astrocytes produce chondroitin sulfate proteoglycans that inhibit axon growth and damage cells. However, neuronal death in the remote area remains controversial. The area of primary injury is the source of numerous neurotoxic molecules that release into the cerebrospinal fluid. It is assumed that these molecules, primarily matrix metalloproteinases, disrupt the blood-spinal cord barrier, which leads to tissue infiltration by macrophage precursors in the remote area. Activated macrophages secrete pro-inflammatory cytokines and matrix metalloproteinases, which, in turn, induce astrocytes and microglia towards a pro-inflammatory phenotype. In addition, reactive microglia, together with astrocytes, secrete numerous pro-inflammatory and neurotoxic molecules that activate inflammatory signaling pathways, consequently exacerbating synaptic depletion and neurological deterioration. It appears likely that the interplay between chronic inflammation and neurodegeneration is a pivotal characteristic of the pathological process in the spinal cord areas distant from the epicenter of the lesion. Pathological changes in the distant areas should be the object of research as potential therapeutic targets.

Convenient in situ synthesis of injectable lysine-contained peptide functionalized hydrogels for spinal cord regeneration

Injectable hydrogels provide a promising strategy to fill the irregular cystic cavity in spinal cord injury. However, a simple and convenient functionalization approach of injectable hydrogels is still a huge challenge. Herein, we report a facile in situ synthetic strategy of injectable lysine-contained peptide functionalized hydrogels for the treatment of spinal cord injury. The ibuprofen-KYIGSRK conjugated hydrogels are in situ synthesized via in situ Michael addition without catalysts and additional reaction-steps. Ibuprofen-KYIGSRK conjugated soft hydrogels promote the adhesion and neurite extension of DRG neurons by upregulating of Sall3, Pou3f3, Lhx5, Shank1 and Sall1. The long-term implanted ibuprofen-KYIGSRK hydrogel is injected into the spinal cord injured site for promoting motor functional recovery. Increased neurites and decreased glial scars are detected with effective functional improvements in footprint. This injectable hydrogel can not only fill the irregular cavities for inhibiting the glial scar formation, but also significantly suppress inflammatory responses and promote nerve regeneration. This study supplies a convenient in situ synthetic route of injectable peptide functionalized hydrogels for the treatment of spinal cord injury or other biomedical applications.

Dorsal root ganglia, neural crest migration, and spinal cord form in snakes

The classic view of the vertebrate dorsal root ganglion is that it arises from trunk neural crest cells that migrate to positions lateral to the spinal cord, sending axons dorsally into the spinal cord and dendrites ventrally to meet with motor axons in the ventral root to form spinal nerves. As a result, the ganglion ends up lying in the dorsal root of the spinal nerve. Serial histological sections of parts of the trunk of juveniles of different snake species revealed that the ganglia lie distal to the junction of dorsal and ventral roots of spinal nerves and outside the neural canal. The anatomical position of spinal ganglia in snakes suggests that regulation of trunk neural crest migration in snakes differs from that in the model endotherms in which it has been most thoroughly explored. Dorsal roots have no distinct rootlets and the span of root entry to the spinal cord is short compared to that of ventral rootlets in the same segment. Comparing early developmental stages to juvenile spinal cords shows an increased separation of spinal nerve root sites and ventral migration of the ganglion in later development. Dorsal rami of the spinal nerves leave directly from the dorsal edge of the ganglion, and the ventral ramus leaves from the ventral tip of the ganglion. How these features relate to the developmental regulation of ganglion form and position and the extraordinary locomotor capabilities of the snake trunk are unclear.

Gold nanodots with stable red fluorescence for rapid dual-mode imaging of spinal cord and injury monitoring.

Spinal cord injury is one of the most devastating complications of spinal surgery, often resulting in numbness, pain or paralysis. Minor injuries in the spinal cord are hard to be identified and existing imaging modalities are unable to provide intraoperative monitoring. Monitoring pathological change at the site of injury is a key factor in staging and treatment decision making as well as prognosis of spinal cord injury. Herein, we offer the fluorescence imaging with intraoperative visualization and detection accuracy for bioimaging to resolve the problem. A novel red fluophore AuNDs caped with glutathione is prepared, which exhibits some advantages such as ultra-small size, negligible biotoxicity, superior water solubility and great biocompatibility. AuNDs fluorophore especially exhibit both of a remarkable photoluminescence stability and high attenuation coefficient to X-rays. In addition, AuNDs can be used as CT contrast agent for spinal cord, which avoid the high toxicity and weak CT signal of traditional iodine contrast. After intradural injection into the spinal cord, AuNDs are transported through the flow of cerebrospinal fluid and bound to the spinal cord parenchyma. not only the bioimage of the entire spinal cord can be achieved as quick as 15min, but they are also particularly beneficial to long-term imaging of complex physiological environments in vivo, with negligible quenching. Comparing from the bright red fluorescence in adjacent normal spinal cord sites, there is almost no fluorescence in spinal cord at the areas of the injury. We suggest that AuNDs are unable to enter the injury sites of necrosis and ischemia, which promote a different contrast imaging from the normal one. The bright red fluorescence of the AuNDs significantly overcome the restriction of the blue autofluorescence of the biological tissues, providing a clear boundary for observation of the thin spinal cord injury. As a result, we developed the AuNDs with fluorescent and CT dual-mode bioimaging capability to clearly and effectively diagnose spinal cord injury, which are expected to provide a novel visualization imaging regent for clinical use.

LRRK‐2 Inhibition By PF06447475 Treatment Reduces Neuronal Damage and Immune Response After Spinal Cord Trauma

Spinal Cord Injury (SCI) is a devastating event followed by neurodegeneration, activation of the inflammatory cascade and immune system. Dysregulated or non‐resolving inflammatory processes can affect neuronal homeostasis and drive immune cells stimulation. The leucine‐rich‐repeat kinase 2 (LRRK2) is a gene associated with the progression of Parkinson’s disease (PD), and its kinase activity was found to be upregulated after instigated inflammation of the Central Nervous System (CNS) and immune system activation. Here, we aimed to investigate the efficacy of PF‐06447475, an LRRK2 inhibitor, by counteracting pathological consequences of spinal cord trauma. The in vivo model of SCI was induced by extradural compression of the spinal cord at T6‐T8 levels, then mice were treated with PF‐06447475 (2.5‐5 and 10 mg/kg o.s) 1 and 6 hrs after SCI. We found that PF‐06447475 treatments at the higher doses (5 and 10 mg/kg) showed great abilities to reduce the degree of spinal cord tissue injury, glycogen accumulation, and demyelination of neurons associated with trauma. In addition, cytokines expression levels including interleukins (IL‐1, IL‐6, IL‐10 and12),interferong(IFN‐g)and tumor necrosis factor‐α (TNF‐α secreted and released by immune cells after trauma were decreased by LRRK‐2 inhibitor treatments. Moreover, the accumulation of CD4+and CD8+cells throughout the spinal cord lesion site of SCI mice was reduced by PF‐06447475 oral administration at the dose of 10 mg/kg. Taken together, our results suggest that exist a mutual correlation between LRRK2, neurodegeneration and immunity and that LRRK2 inhibition could have direct effects on the intervention of neuroinflammatory disorders.

Alginate hydrogel cross-linked by Ca2+ to promote spinal cord neural stem/progenitor cell differentiation and functional recovery after a spinal cord injuryhh.

Alginate capillary hydrogels seeded with differentiated cells can fill the lesion cavity and promote axonal regeneration after grafting into the injured spinal cord. Neural stem/progenitor cells (NSPCs) can potentially repair the spinal cord; however, effects of alginate hydrogels (AHs) on NSPCs remain unknown. In this study, we fabricated AHs cross-linked by Ca2+ and seeded hydrogels with rat embryonic day 14 NSPCs. Immunocytochemistry and electron microscopy show that NSPCs survive, proliferate and differentiate into neurons in vitro within the capillaries. After transplantation into an acute T8 complete spinal cord transection site in adult rats, approximately one-third (38.3%) of grafted cells survive and differentiate into neurons (40.7%), astrocytes (26.6%) and oligodendrocytes (28.4%) at 8 weeks post-grafting. NSPCs promote the growth of host axons within the capillaries in a time-dependent manner. Host axons make synapse-like contacts with NSPC-derived neurons within the hydrogel channels, and graft-derived axons extend into the host white and gray matter making putative synapses. This is paralleled by improved electrophysiological conductivity across the lesion and partial hindlimb locomotor recovery.

Evaluation of [18F]F-DPA PET for Detecting Microglial Activation in the Spinal Cord of a Rat Model of Neuropathic Pain

PurposeRecent studies have linked activated spinal glia to neuropathic pain. Here, using a positron emission tomography (PET) scanner with high spatial resolution and sensitivity, we evaluated the feasibility and sensitivity of N,N-diethyl-2-(2-(4-([18F]fluoro)phenyl)-5,7-dimethylpyrazolo[1,5-a] pyrimidin-3-yl)acetamide ([18F]F-DPA) imaging for detecting spinal cord microglial activation after partial sciatic nerve ligation (PSNL) in rats.ProceduresNeuropathic pain was induced in rats (n = 20) by PSNL, and pain sensation tests were conducted before surgery and 3 and 7 days post-injury. On day 7, in vivo PET imaging and ex vivo autoradiography were performed using [18F]F-DPA or [11C]PK11195. Ex vivo biodistribution and PET imaging of the removed spinal cord were carried out with [18F]F-DPA. Sham-operated and PK11195-pretreated animals were also examined.ResultsMechanical allodynia was confirmed in the PSNL rats from day 3 through day 7. Ex vivo autoradiography showed a higher lesion-to-background uptake with [18F]F-DPA compared with [11C]PK11195. Ex vivo PET imaging of the removed spinal cord showed [18F]F-DPA accumulation in the inflammation site, which was immunohistochemically confirmed to coincide with microglia activation. Pretreatment with PK11195 eliminated the uptake. The SUV values of in vivo [18F]F-DPA and [11C]PK11195 PET were not significantly increased in the lesion compared with the reference region, and were fivefold higher than the values obtained from the ex vivo data. Ex vivo biodistribution revealed a twofold higher [18F]F-DPA uptake in the vertebral body compared to that seen in the bone from the skull.Conclusions[18F]F-DPA aided visualization of the spinal cord inflammation site in PSNL rats on ex vivo autoradiography and was superior to [11C]PK11195. In vivo [18F]F-DPA PET did not allow for visualization of tracer accumulation even using a high-spatial-resolution PET scanner. The main reason for this result was due to insufficient SUVs in the spinal cord region as compared with the background noise, in addition to a spillover from the vertebral body.

Lumbar surgical drains do not increase the risk of infections in patients undergoing spine surgery.

The aim of this study was to characterize if the use of surgical drains or length of drain placement following spine surgery increases the risk of post-operative infection. Records of patients undergoing elective spinal surgery at a tertiary care center were collected between May 5, 2016 and August 16, 2018. Pre-operative baseline characteristics were recorded including patient's demographics and comorbidities. Intraoperative procedure information was documented related to procedure type, blood loss, and antibiotics used. Following surgery, patients were then further subdivided into two groups: patients who were discharged with a spinal surgical site drain and patients who did not receive a drain. Post-operative surgical variables included length of stay (LOS), drain length, number of antibiotics given, and type of post-operative infection. Univariate and multivariate statistical analysis was conducted. A total of 671 patients were included in the current study, 386 (57.5%) with and 285 (42.5%) without the drain. The overall infection rate was 5.7% with 6.22% among patients with the drain compared to 4.91% in patients without drain. The univariate analysis identified the following variables to be significantly associated with the infection: total number of surgical levels, spinal region, blood loss, redosing of antibiotics, length of stay, length of drain placement, and number of antibiotics (P < 0.05). However, the multivariate analysis none of the predictors was significant. The current study shows that the placement of drain does not increase rate of infection, irrespective of levels, length of surgery, or approach.

This Month in Anesthesiology

This Month in Anesthesiology

The functional properties of synapses made by regenerated axons across spinal cord lesion sites in lamprey.

While the anatomical properties of regenerated axons across spinal cord lesion sites have been studied extensively, little is known of how the functional properties of regenerated synapses compared to those in unlesioned animals. This study aims to compare the properties of synapses made by regenerated axons with unlesioned axons using the lamprey, a model system for spinal injury research, in which functional locomotor recovery after spinal cord lesions is associated with axonal regeneration across the lesion site. Regenerated synapses below the lesion site did not differ from synapses from unlesioned axons with respect to the amplitude and duration of single excitatory postsynaptic potentials. They also showed the same activity-dependent depression over spike trains. However, regenerated synapses did differ from unlesioned synapses as the estimated number of synaptic vesicles was greater and there was evidence for increased postsynaptic quantal amplitude. For axons above the lesion site, the amplitude and duration of single synaptic inputs also did not differ significantly from unlesioned animals. However, in this case, there was evidence of a reduction in release probability and inputs facilitated rather than depressed over spike trains. Synaptic inputs from single regenerated axons below the lesion site thus do not increase in amplitude to compensate for the reduced number of descending axons after functional recovery. However, the postsynaptic input was maintained at the unlesioned level using different synaptic properties. Conversely, the facilitation from the same initial amplitude above the lesion site made the synaptic input over spike trains functionally stronger. This may help to increase propriospinal activity across the lesion site to compensate for the lesion-induced reduction in supraspinal inputs. The animal experiments were approved by the Animal Ethics Committee of Cambridge University.