Ginsenoside Rg1-induced activation of astrocytes promotes functional recovery via the PI3K/Akt signaling pathway following spinal cord injury.

AIMS: To determine whether ginsenoside Rg1 is involved in scratch wound healing through altered expression of related molecules in astrocytes and improved functional recovery after spinal cord injury (SCI). MATERIALS AND METHODS: Astrocytes were isolated from rats, followed by Rg1 treatment. The wound healing test was performed to observe the scratch wound healing in different groups. The expression of nerve growth factor (NGF), glial cell line-derived neurotrophic factor (GDNF), basic fibroblast growth factor (bFGF), and components of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway were detected by western blot. Reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the altered expression of laminin (LN) and fibronectin (FN). A revised Allen's method for the SCI model was performed, followed by Rg1 treatment. Then, functional scoring was conducted to evaluate the functional recovery. Hematoxylin-eosin (HE) staining showed changes in the void area. Finally, western blot assessed the expression of glial fibrillary acidic protein (GFAP) and chondroitin sulfate proteoglycans (CSPGs). KEY FINDINGS: Rg1 mediated scratch wound healing through inducing an increased release of LN, FN, NGF, GDNF, and bFGF in vitro. Additionally, Rg1 activated the PI3K/Akt signaling pathway and promoted the functional recovery of hindlimb movement in rats. Furthermore, Rg1 significantly reduced the void area and downregulated the expression of GFAP and CSPGs. SIGNIFICANCE: Rg1 not only enhanced the scratch wound repair in vitro through the release of astroglial neurotrophic factors, adhesion factors, and inhibitory factors, but it also improved the functional recovery in vivo following SCI.

Relationship Between Modic Changes and Sagittal Balance Parameters in the Cervical Spine.

BACKGROUND We explored the possible relationship between Modic changes (MCs) and sagittal parameters of the cervical spine. MATERIAL AND METHODS We enrolled 150 patients with cervical MC on the magnetic resonance imaging (MRI) scans in the MC (+) group and divided them into 3 sub-groups with 50 patients each: the MC1 sub-group, the MC2 sub-group, and the MC3 sub-group. Another 150 healthy subjects receiving routine health examinations were also enrolled in the study as the MC (-) group. The sagittal parameters in the cervical spine were measured and compared and multiple logistic regression analysis was performed to analyze the risk factor for the occurrence of MC. RESULTS Four cervical sagittal parameters were measured and compared between all the enrolled groups, including neck tilt (NT), T1 slope (T1s), thoracic inlet angle (TIA), and Cobb C2-C7. The results confirmed that the parameter of Cobb C2-C7 was much smaller in the MC(+) group when compared with that in the MC(-) group (P<0.05), while no significant differences were detected between the MC(+) and MC(-) groups for the parameters of NT, T1 T1s, and TIA (P>0.05). Multiple logistic regression analysis showed that Cobb C2-C7 (less than 8.5°) could be regarded as the risk factor for the occurrence of MC, and the receiver operating characteristic (ROC) curve showed that moderate diagnostic significance was obtained with an area under curve (AUC) of 0.82. CONCLUSIONS The present study demonstrated that Cobb C2-C7 (less than 8.5°) is a potential risk factor for the development of MC.

Negative Pressure Therapy in the Regeneration of the Sciatic Nerve Using Vacuum - Assisted Closure in a Rabbit Model.

BACKGROUND The aim of this study was to investigate the effects of negative pressure therapy in the regeneration of the rabbit sciatic nerve using vacuum assisted closure (VAC). MATERIAL AND METHODS Thirty male New Zealand white rabbits underwent surgical injury of the sciatic nerve, followed by negative pressure therapy using vacuum assisted closure (VAC), in three treatment groups: Group A: 0 kPa; Group B: -20 kPa; Group C: -40 kPa. At 12 weeks following surgery, the following factors were studied: motor nerve conduction velocity (MNCV); the number of myelinated nerve fibers; the wet weight of the gastrocnemius muscle. Gastrocnemius muscle and sciatic nerve tissue samples were studied for the expression of S100, and brain-derived neurotrophic factor (BDNF) using Western blot. RESULTS At 12 weeks following VAC treatment, the MNCV, number of myelinated nerve fibers, and wet weight of the gastrocnemius muscle showed significant differences between the groups (p<0.05), in the following order: Group B >Group A >Group C. The sciatic nerve at 12 weeks following VAC in Group B and Group C showed a significant increase in expression of S100 and BDNF when compared with Group A; no significant differences were detected between Group B and Group C results from Western blot at 12 weeks. CONCLUSIONS The findings of this study, using negative pressure therapy in VAC in a rabbit model of sciatic nerve damage, have shown that moderate negative pressure was beneficial, but high values did not benefit sciatic nerve repair.

Ginsenoside Rg1 Promotes the Migration of Olfactory Ensheathing Cells via the PI3K/Akt Pathway to Repair Rat Spinal Cord Injury.

The aim of this study was to determine the effects of ginsenoside Rg1 on the migration of olfactory ensheathing cells (OECs) in vitro, and its influence on the therapeutic efficacy of OECs transplanted in vivo for the treatment of spinal cord injury (SCI). Primary cultured and purified OECs (prepared from rats) were treated with ginsenoside Rg1. The wound healing test indicated that ginsenoside Rg1 promoted the migration of OECs. Real-time RT-PCR demonstrated that ginsenoside Rg1 upregulated the expression of migration-related factors of OECs, including matrix metalloproteinases-2 (MMP-2), MMP-9, and neural cell adhesion molecule 1 (NCAM1). Moreover, Western blot analysis indicated that ginsenoside Rg1 significantly promoted the migration of OECs via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. An SCI rat model was induced in vivo using a revised Allen's method. The Basso, Beattie, and Bresnahan (BBB) scores and histological analysis demonstrated that OECs, which were treated with ginsenoside Rg1, exhibited significant improvement in SCI compared with both the control group and the OEC group. Thus, ginsenoside Rg1 may represent a novel treatment target for SCI.

Static Compression Induces ECM Remodeling and Integrin α2ß1 Expression and Signaling in a Rat Tail Caudal Intervertebral Disc Degeneration Model.

STUDY DESIGN: A three-level rat tail caudal intervertebral disc (IVD) degeneration (IVDD) model was established to study effects of static compression on extracellular matrix (ECM) remodeling and integrin signaling in IVDs during IVDD. OBJECTIVE: The aim of this study was to investigate the effect of compression force on ECM remodeling and integrin signaling in IVDs during IVDD. SUMMARY OF BACKGROUND DATA: Integrins sense mechanical environment alteration via binding to ECM ligands and trigger intracellular signaling for pathological ECM remodeling during IVDD. However, the role of compression force in ECM remodeling and integrin signaling during IVDD remains elusive. METHODS: Compared with the classical one-level rat tail IVDD model that exerts axial stress on the 8th to 9th caudal vertebral bodies, a three-level model was established by using an Ilizarov-type apparatus to exert stress on the 7th to 10th caudal vertebral bodies in rat tails for four weeks. To exclude side effects from surgical stab injury on manipulated discs, intact coccygeal (Co) disc Co8-9 was analyzed. RESULTS: In three-level IVDD model, significant degeneration of the Co8-9 disc was observed. Quantitative real-time polymerase chain reaction (qRT-PCR) showed elevated mRNA expression of collagen types I, III, and V; matrix metalloproteinases (MMPs) 2, 3, 9, 13, 14; and decreased mRNA expression of collagen type II in Co8-9 disc. Compression loading altered the expression of integrin α2ß1 (upregulated) and α10ß1 (downregulated) in NP cells, and activated integrin downstream signaling. By contrast, one-level model showed more severe disc degeneration and ECM remodeling. Integrin α1, α2, α11, and ß1 were upregulated, whereas α10 was downregulated. Similar activation of integrin signaling was observed. CONCLUSION: Static compression altered collagen and MMP expression, and promoted ß1 integrin expression and signaling in IVD. Compared with one-level rat tail IVDD model, three-level model showed milder effects on disc degeneration, ECM remodeling, and integrin expression, suggesting one-level model might involve other causes that induce IVDD via mechanisms independent of compression force. LEVEL OF EVIDENCE: N/A.

Follistatin-like 1 attenuates differentiation and survival of erythroid cells through Smad2/3 signaling.

Hematopoiesis is a complex process tightly controlled by sets of transcription factors in a context-dependent and stage-specific manner. Smad2/3 transcription factor plays a central role in differentiation and survival of erythroid cells. Here we report that follistatin-like 1 (FSTL1) treatment impairs hemin-induced erythroid differentiation and cell survival. FSTL1 differentially regulates transforming growth factor beta (TGF-ß) and bone morphogenetic protein (BMP) signaling. Blockade of Smad2/3 signaling with the ALK5/type I TGF-ßR kinase inhibitor, SB-525334, was efficacious for rescue of erythroid differentiation blockage and apoptosis. Reversely, activation of Smad1/5/8 signaling with BMP4 cannot rescue FSTL1-mediated erythroid differentiation blockage and apoptosis. Collectively, these data provide mechanistic insight into the regulation of erythropoiesis by FSTL1 signaling and lay a foundation for exploring FSTL1 signaling as a therapeutic target for anemia.

Coblation nucleoplasty for adjacent segment degeneration after posterolateral fusion surgery: a case report.

BACKGROUND AND OBJECTIVES: Symptomatic ASD after lumbar spinal fusion surgery occurs most commonly in the cranial segment. The surgery for ASD contains anterior lumbar interbody fusion, posterior lumbar interbody fusion, decompression alone (laminotomy) and so on. But coblation nucleoplasty for ASD has not been reported previously. In this study, a case of coblation nucleoplasty after posterolateral fusion surgery at L4-L5 for adjacent segment degeneration (ASD) was reported and the clinical results were examined. MATERIAL AND METHOD: A 32-year-old male patient who had discectomy and fusion on the L4-L5 level seven years ago complained of chronic back pain for four months with numbness on his right leg for a month. X-ray revealed mild lumbar instability on L3-L4 segment. Magnetic resonance imaging confirmed a right-sided L3-L4 herniated disc compressing the L4 nerve root. He underwent L3-L4 coblation nucleoplasty. The visual analog scale (VAS) was adopted to assess the relief of back pain, leg pain and numbness. RESULTS: The operation was performed successfully and the symptoms were relieved significantly at the follow-up of more than twenty-four months. CONCLUSION: Although coblation nucleoplasty is not a regular therapy for ASD, the excellent outcome of this case suggests that this technique might be an option before a complicated revision surgery.

The efficacy of coblation nucleoplasty for protrusion of lumbar intervertebral disc at a two-year follow-up.

PURPOSE: The purpose of this study was to evaluate longer-term efficacy over a two-year follow-up of coblation nucleoplasty treatment for protruded lumbar intervertebral disc. METHODS: Forty-two cases of protruded lumbar intervertebral disc treated by coblation nucleoplasty followed-up for two years were analysed. Relief of low back pain, leg pain and numbness after the operation were assessed by visual analogue pain scale (VAS). Function of lower limb and daily living of patients were evaluated by the Oswestry Disability Index (ODI). RESULTS: Operations were performed successfully in all cases. Three patients had recurrence within a week of the procedure. Evaluation of the 42 patients demonstrated significant improvement rate of VAS: defined as 66.2% in back pain, 68.1% in leg pain, and 85.7% in numbness at one-week after the operation; 53.2%, 58.4%, 81.0% at one-year; and 45.5%, 50.7%, 75.0% at two-year follow-up. One week after the operation, obvious amelioration occurred in all the patients, but the tendency decreased. Before operation, the mean value of ODI was 68.2 ± 10.9%. The value at one week was 28.6 ± 8.2%; one-year at 35.8 ± 6.5%; and two-years at 39.4 ± 5.8%. CONCLUSION: Coblation nucleoplasty may have satisfactory clinical outcomes for treatment of protruded lumbar intervertebral disc for as long as two-year follow-up, but longer-term benefit still needs verification.

Ginsenoside Rg1 promotes proliferation and neurotrophin expression of olfactory ensheathing cells.

Transplantation of olfactory ensheathing cells (OECs) is currently considered to be one of the most promising repair strategies for human spinal cord injury. However, the factors that regulate OECs are still poorly understood. Ginsenoside Rg1 (Rg1), the phytosterol from Panax ginseng, is a potent neuroprotective agent that promotes axonal regeneration. The aim of this study is to determine whether Rg1 would influence the biological activity of OECs. Primary cultured OECs from the olfactory bulb of neonatal rats were treated with Rg1 of various concentrations and durations. Using MTT and bromodeoxyuridine assays, we found that Rg1 significantly promoted cell proliferation, with an optimal concentration of 40 mug/ml of Rg1 at 72 h. In addition, RT-PCR and ELISA assays showed that Rg1 could upregulate the mRNA expression and secretion of glial cell-derived neurotrophic factor, brain-derived neurotrophic factor, and nerve growth factor. These results suggest that Rg1 may have a great potential in OEC therapy.

Effectiveness of postural and instrumental reduction in the treatment of thoracolumbar vertebra fracture.

We compared the effectiveness of postural reduction and instrumental reduction in the treatment of thoracolumbar and lumbar vertebra fracture in 40 patients. Under general anaesthesia, postural reduction in a stretching prone position was first performed. Instrumental reduction and fixation were then conducted. Radiographs were made after each reduction. Comparisons between the two films and the fracture films were made based on the changes in prevertebral height of both the fractured vertebra and the adjacent superior and inferior intervertebral spaces. It was found that the recovery of the prevertebral height in postural and instrumental reductions was basically identical. The recovery of the prevertebral height in the intervertebral spaces was more significant in instrumental reduction. Both reductions were ineffective in patients whose compression of the diseased vertebra was more than two-thirds of the normal. In cases of lower lumbar vertebra fractures, the effect of both reductions was unsatisfactory. Our findings indicated that the effectiveness of the reduction of vertebra fracture depends on the quantitative change of the spongy bone of the injured vertebra. Instrumental reduction only exerts an indirect tension. Postural reduction is effective in reducing thoracolumbar vertebral fracture, while instrumental reduction exerts only a relatively weak effect but it is particularly useful to maintain the result of postural reduction.

[Diagnosis and operative treatment of far lateral lumbar disc herniation].

OBJECTIVE: To discuss the characteristics and operative selection of far lateral lumbar disc herniation (FLLDH). METHODS: Twenty-three cases of FLLDH, 14 were foraminal, and 9 were extraforaminal lumbar disc herniation. Of the 23 cases, low back pain was observed in 8 cases (31%), severe lower leg pain in 21 cases (91%) and Lasegue sign in 10 cases (43%). CT and MRI showed the protruded disc in and outside of the foramen clearly. Three surgical procedures were performed, including hemilaminotomy with medial facetectomy, facetectomy with pedicle screw fixation and fusion with posteolateral bone grafting, and the transmuscular approaches. RESULTS: Twenty-two cases were followed up for an average of 3.6 years. According to the Macnab criteria, 15 patients achieved excellent results, good 4, fair 3 and poor 0. Excellent and good rate was 86%. CONCLUSIONS: The symptoms and signs of FLLDH mainly result from injury of upper nerve segments with the dominant symptom of severe lower leg pain. CT and MRI appearance are not only sensitive but also specific for the diagnosis of FLLDH. In foraminal lumbar disc herniation, the hemilaminotomy with medial facetectomy is recommended. While in extraforaminal lumbar disc herniation, either facetectomy with pedicle screw fixation and fusion with posterolateral bone grafting or transmuscular approaches for removal of nucleus pulposus can be chosen. Microendoscopic discectomy is a new, safe and efficient method for the disease, however, a skillful microendoscopic technique should be mastered prior.