Detailed Anatomy for the Transoral Approach to the Craniovertebral Junction: An Exposure and Safety Study

Objective The aim of this study was to demonstrate the anatomical structures of the transoral approach to the craniovertebral junction. We evaluated the necessary exposure field and the safety of this approach. Methods Surgical operations with the transoral approach were performed on 36 cadaver specimens. The special anatomical structures were measured surrounding the exposure field with priorities given to measurements relating to the vertebral artery (VA). The anatomical relationships between the VA and nerves were observed. Results The exposure field partly covered the vertebral basilar system confluent. The middle clivus to upper C3 vertebral body can be exposed by transoral approach. Cranial nerves and cervical nerves emerged from the caudal of vertebrobasilar artery and circumambulated anterolaterally, and some abnormalities were observed in the intracranial segment of vertebrobasilar artery. The safe field was in an inverted trapezoid shape, of which the widest point was 25.5 ± 4.5 mm to the midline at C1 transverse process level; the narrowest point was 11.2 ± 1.5 mm to the midline at the C2-3 level. Conclusion Because the VA is the landmark of the safe field in this approach, surgeons should be very careful to avoid injuries of the VA and nerves while operating in the intracranial field or at the C2-3 level

Detailed Anatomy for the Transoral Approach to the Craniovertebral Junction: An Exposure and Safety Study

Objective The aim of this study was to demonstrate the anatomical structures of the transoral approach to the craniovertebral junction. We evaluated the necessary exposure field and the safety of this approach. Methods Surgical operations with the transoral approach were performed on 36 cadaver specimens. The special anatomical structures were measured surrounding the exposure field with priorities given to measurements relating to the vertebral artery (VA). The anatomical relationships between the VA and nerves were observed. Results The exposure field partly covered the vertebral basilar system confluent. The middle clivus to upper C3 vertebral body can be exposed by transoral approach. Cranial nerves and cervical nerves emerged from the caudal of vertebrobasilar artery and circumambulated anterolaterally, and some abnormalities were observed in the intracranial segment of vertebrobasilar artery. The safe field was in an inverted trapezoid shape, of which the widest point was 25.5 ± 4.5 mm to the midline at C1 transverse process level; the narrowest point was 11.2 ± 1.5 mm to the midline at the C2–3 level. Conclusion Because the VA is the landmark of the safe field in this approach, surgeons should be very careful to avoid injuries of the VA and nerves while operating in the intracranial field or at the C2–3 level

Reciprocal Interferences of TNF-α and Wnt1/β-Catenin Signaling Axes Shift Bone Marrow-Derived Stem Cells Towards Osteoblast Lineage after Ethanol Exposure

Background/Aims: We have reported in a separate study that alcohol exposure triggers activation of the TNF-α signaling pathway leading to an adverse shift of multipotential mesenchymal stem cells in bone marrow (BMSCs) away from osteogenesis towards adipogenesis. However, inhibition of TNF-α signaling only yielded moderate inhibition of adipogenesis. Here we showed that in addition to promoting the TNF-α signaling, alcohol also suppressed the Wnt1/β-catenin signaling pathway. Methods: We treated primary BMSCs from human subjects with alcohol for 24 days. We measured changes of genes related to endoplasmic reticulum (ER) stress, adipogenic markers and osteogenic markers using quantitative real-time RT-PCR and Western blot analysis. We performed Alizarin red staining for osteogenesis. We also conducted assays for osteogenic biomarkers alkaline phosphatase, collagen-I and osteocalcin. Results: Wnt/β-catenin signaling was markedly activated in BMSCs treated with osteogenic inducers relative to the control cells, as indicated by the increased levels of nuclear β-catenin along with reduced levels of cytosolic β-catenin, as well as increased protein levels of Wnt1. Activation of Wnt/β-catenin signaling was significantly suppressed in BMSCs exposed to alcohol, which was reflected by downregulated expression of osteogenic marker genes Osf2/Cbfa1, osteopontin and osteocalcin, upregulated adipogenic marker PPARγ2 and aP2, and reduced number of calcifcation nodules. In contrast, activation of Wnt/β-catenin signaling by BIO favored osteogenesis even in the presence of alcohol. Simultaneous activation of Wnt1 by BIO and inhibition of TNF-α by 3,6'-dithiothalidomide produced synergetic suppression of ethanol-induced adipogenic lineage compared to interference with either of them alone. Conclusion: This remarkable shift of BMSCs towards osteoblast lineage suggests the superiority of concordant and reciprocal interferences of the TNF-α and Wnt/β-catenin pathways for promoting osteogenesis

ER Stress Activating ATF4/CHOP-TNF-α Signaling Pathway Contributes to Alcohol-Induced Disruption of Osteogenic Lineage of Multipotential Mesenchymal Stem Cell

Background/Aims: Studies have provided substantial evidence that osteoblasts and adipocytes share common progenitor‒multipotential mesenchymal stem cells in bone marrow (BMSCs), and excessive alcohol consumption shifts away from osteogenic to adipogenic lineage. However, how exactly alcohol impairs osteogenesis is still incompletely understood. This study was designed to shed light on this issue. Methods: We treated primary BMSCs from human subjects with alcohol for 24 days. We measured changes of genes related to endoplasmic reticulum (ER) stress, adipogenic markers and osteogenic markers using quantitative real-time RT-PCR and Western blot analysis. We performed Oil red O staining and quantification of adipogenesis. We also conducted caspase 3 activity assay to assess BMSC apoptosis. Results: We showed here that chronic exposure of BMSCs to alcohol induced adipogenesis and disrupted osteogenesis as indicated by upregulation of adipogenic markers (PPARγ2 and aP2), downregulation of osteogenic markers (Osf2/Cbfa1), and accumulation of lipid droplets. Alcohol induced ER stress, as reflected by increased expression of glucose-regulated proteins GRP78 and GRP94, and by increased expression of transcription factors activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP), and enhanced caspase 3 activity. Additionally, ER stress also upregulated tumor necrosis factor-alpha (TNF-α). Simultaneous silencing of ATF4 and CHOP prevented upregulation of TNF-α. Knockdown of either ATF4 and CHOP or TNF-α by their siRNAs was able to reverse the ethanol-induced adipogenesis. Conclusion: Our data therefore revealed a role of ER stress and ATF4/CHOP in the ethanol-induced inhibition of osteogenesis, and activation of TNF-α signaling by ATF4/CHOP linking ER stress to adipogenic lineage in response to alcohol stimulation. This work should establish a new signaling pathway linking alcohol, ER stress, and TNF-α to loss of bone formation: Ethanol → ER stress↑↑↑ → ATF4 & CHOP↑↑↑ → TNF-α↑↑↑ → Osteoblasts↓↓↓

An antibacterial and absorbable silk-based fixation material with impressive mechanical properties and biocompatibility

Implant-associated infections and non-absorbing materials are two important reasons for a second surgical procedure to remove internal fixation devices after an orthopedic internal fixation surgery. The objective of this study was to produce an antibacterial and absorbable fixation screw by adding gentamicin to silk-based materials. The antibacterial activity was assessed against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) in vitro by plate cultivation and scanning electron microscopy (SEM). We also investigated the properties, such as the mechanical features, swelling properties, biocompatibility and degradation, of gentamicin-loaded silk-based screws (GSS) in vitro. The GSS showed significant bactericidal effects against S. aureus and E. coli. The antibacterial activity remained high even after 4 weeks of immersion in protease solution. In addition, the GSS maintained the remarkable mechanical properties and excellent biocompatibility of pure silk-based screws (PSS). Interestingly, after gentamicin incorporation, the degradation rate and water-absorbing capacity increased and decreased, respectively. These GSS provide both impressive material properties and antibacterial activity and have great potential for use in orthopedic implants to reduce the incidence of second surgeries