Cell-Free Extracts from Human Fat Tissue with a Hyaluronan-Based Hydrogel Attenuate Inflammation in a Spinal Cord Injury Model through M2 Microglia/Microphage Polarization.

Treatment for spinal cord injuries (SCIs) is often ineffective because SCIs result in a loss of nerve tissue, glial scar formation, local ischemia and secondary inflammation. The current promising strategy for SCI is the combination of bioactive materials and cytokines. Bioactive materials support the injured spinal cord, stabilize the morphology, and avoid excessive inflammatory responses. Fat extract (FE) is a cell-free liquid component containing a variety of cytokines extracted from human fat tissue using mechanical methods. In this research, a biocompatible HAMC (hyaluronan and methylcellulose) loaded with FE is used to treat a model of spinal cord contusion in mice. The composite not only inhibits death of neuro- and vascular cells and leads to the preservation of neural and vascular structure, but also modulates the inflammatory phenotype of macrophages in the locally injured region. Specifically, FE promotes the polarization of macrophages from an inflammatory M1 phenotype to an anti-inflammatory M2 phenotype. During the screening of the involved pathways, it is corroborated that activation of the STAT6/Arg-1 signaling pathway is involved in macrophage M2 polarization. In summary, FE is a promising treatment for SCI, as it is easy to obtain, nonimmunogenic, and effective.

CircularRNA_104670 plays a critical role in intervertebral disc degeneration by functioning as a ceRNA.

This study was carried out to explore the roles of circular RNAs (circRNAs) in nucleus pulposus (NP) tissues in intervertebral disc degeneration (IDD). Differentially expressed circRNAs in IDD and normal NP tissues were identified based on the results of microarray analysis. Bioinformatics techniques were employed to predict the direct interactions of selected circRNAs, microRNAs (miR), and mRNAs. CircRNA_104670 was selected as the target circRNA due to its large multiplier expression in IDD tissues. After luciferase reporter and EGFP/RFP reporter assays, we confirmed that circRNA_104670 directly bound to miR-17-3p, while MMP-2 was the direct target of miR-17-3p. The receiver-operating characteristic (ROC) curve showed that circRNA_104670 and miR-17-3p had good diagnostic significance for IDD (AUC circRNA_104670 = 0.96; AUC miRNA-17-3p = 0.91). A significant correlation was detected between the Pfirrmann grade and expression of circRNA_104670 (r = 0.63; p = 0.00) and miR-17-3p (r = -0.62; p = 0.00). Flow-cytometric analysis and the MTT assay showed that interfering with circRNA_104670 using small interfering RNA (siRNA) inhibited NP cell apoptosis (p < 0.01), and this inhibition was reduced by interfering with miR-17-3p. Interfering with circRNA_104670 suppressed MMP-2 expression and increased extracellular matrix (ECM) formation, which were also reduced by interfering with miR-17-3p. Finally, an MRI evaluation showed that circRNA_104670 inhibition mice had a lower IDD grade compared with control mice (p < 0.01), whereas circRNA_104670 and miRNA-17-3p inhibition mice had a higher IDD grade compared with circRNA_104670 inhibition mice (p < 0.05). CircRNA_104670 is highly expressed in the NP tissues of IDD and acts as a ceRNA during NP degradation.

Cortical Activation Changes in Hirayama Disease After Anterior Cervical Decompression and Fusion.

BACKGROUND: Spinal cord injury may cause cortical reconstruction. We, therefore explored the changes in cortical activation before and after anterior cervical decompression and fusion surgery in patients with Hirayama disease (HD). METHODS: In total, 17 cases with HD underwent anterior cervical decompression and fusion surgery. Blood oxygenation level-dependent functional magnetic resonance imaging scan was performed preoperatively, 3 months, 6 months, and 1 year after surgery. Activated voxels were compared between both hands after adjusting for head motion, slice timing, spatial normalization, and image smoothing. Grip strength also was tested in both hands. RESULTS: A retrospective review indicated that the grip strength of the asymptomatic hand was significantly stronger than the symptomatic hand at the time point before the surgery, 3 months after surgery, 6 months after surgery, and 1 year after surgery (P < 0.001). The grip strength of both symptomatic and asymptomatic hands continuously increased within 6 months after surgery (P < 0.05), but it stopped at 1 year after the surgery. The symptomatic limb tends to produce bilateral activation in the primary motor area (M1) during motor tasks. Both contralateral and ipsilateral M1 activation were stronger in symptomatic hand tasks preoperatively (P < 0.05). Both contralateral and ipsilateral activation in M1 during symptomatic hand tasks began to reduce after surgery, and statistical significance was observed 6 months after surgery (P < 0.05). Contralateral activation was relatively even over 6 months of the surgery (P > 0.05). CONCLUSIONS: After surgery, pathologic reconstruction may have occurred in the primary motor cortex. Recovery of motor function in the symptomatic limb was accompanied by decreased ipsilateral and contralateral M1 activation, as well as symptom improvement. These findings suggested that postoperative cortical activation changes may reflect functional recovery in HD.

The value of radiographic indexes in the diagnosis of discogenic low back pain: a retrospective analysis of imaging results.

To explore value of different radiographic indexes in the diagnosis of discogenic low back pain (LBP). A total number of 120 cases (60 patients diagnosed with discogenic LBP and 60 healthy people) were retrospectively analysed to identify factors in the diagnosis of discogenic LBP by using univariate and multivariate analyses. A receiver operating characteristic (ROC) curve was drew to show the predictive accuracy of the finally enrolled factors. Among all the included patients, 60 were strictly admitted in the discogenic LBP group while the other 60 were enrolled in the control group. Five results shows significant differences between discogenic LBP and control groups, including Cobb angle, lumbar stability, height of the disc, Modic change and High intense zone (HIZ) based on the results of univariate analysis; lumbar stability, Modic change and HIZ show high value in the diagnosis of lumbar discogenic pain based on the multivariate logistic analysis. The ROC curve shows that good diagnostic accuracy was obtained from the enrolled diagnostic factors including lumbar stability (Angular motion, more than 14.35°), Modic change and HIZ.

Can an Endplate-conformed Cervical Cage Provide a Better Biomechanical Environment than a Typical Non-conformed Cage?: A Finite Element Model and Cadaver Study.

OBJECTIVES: To evaluate the biomechanical characteristics of endplate-conformed cervical cages by finite element method (FEM) analysis and cadaver study. METHODS: Twelve specimens (C2 -C7 ) and a finite element model (C3 -C7 ) were subjected to biomechanical evaluations. In the cadaver study, specimens were randomly assigned to intact (I), endplate-conformed (C) and non-conformed (N) groups with C4-5 discs as the treated segments. The morphologies of the endplate-conformed cages were individualized according to CT images of group C and the cages fabricated with a 3-D printer. The non-conformed cages were wedge-shaped and similar to commercially available grafts. Axial pre-compression loads of 73.6 N and moment of 1.8 Nm were used to simulate flexion (FLE), extension (EXT), lateral bending (LB) and axial rotation (AR). Range of motion (ROM) at C4-5 of each specimen was recorded and film sensors fixed between the cages and C5 superior endplates were used to detect interface stress. A finite element model was built based on the CT data of a healthy male volunteer. The morphologies of the endplate-conformed and wedge-shaped, non-conformed cervical cages were both simulated by a reverse engineering technique and implanted at the segment of C4-5 in the finite element model for biomechanical evaluation. Force loading and grouping were similar to those applied in the cadaver study. ROM of C4-5 in group I were recorded to validate the finite element model. Additionally, maximum cage-endplate interface stresses, stress distribution contours on adjoining endplates, intra-disc stresses and facet loadings at adjacent segments were measured and compared between groups. RESULTS: In the cadaver study, Group C showed a much lower interface stress in all directions of motion (all P < 0.05) and the ROM of C4-5 was smaller in FLE-EXT (P = 0.001) but larger in AR (P = 0.017). FEM analysis produced similar results: the model implanted with an endplate-conformed cage presented a lower interface stress with a more uniform stress distribution than that implanted with a non-conformed cage. Additionally, intra-disc stress and facet loading at the adjacent segments were obviously increased in both groups C and N, especially those at the supra-jacent segments. However, stress increase was milder in group C than in group N for all directions of motion. CONCLUSIONS: Endplate-conformed cages can decrease cage-endplate interface stress in all directions of motion and increase cervical stability in FLE-EXT. Additionally, adjacent segments are possibly protected because intra-disc stress and facet loading are smaller after endplate-conformed cage implantation. However, axial stability was reduced in group C, indicating that endplate-conformed cage should not be used alone and an anterior plate system is still important in anterior cervical discectomy and fusion.

Mast Quadrant-assisted minimally invasive modified transforaminal lumbar interbody fusion: single incision versus double incision.

BACKGROUND: The concept of minimally invasive techniques is to make every effort to reduce tissue damage. Certainly, reducing skin incision is an important part of these techniques. This study aimed to investigate the clinical feasibility of Mast Quadrant-assisted modified transforaminal lumbar interbody fusion (TLIF) with a small single posterior median incision. METHODS: During the period of March 2011 to March 2012, 34 patients with single-segment degenerative lumbar disease underwent the minimally invasive modified TLIF assisted by Mast Quadrant with a small single posterior median incision (single incision group). The cases in this group were compared to 37 patients with single-segment degenerative lumbar disease in the double incision group. The perioperative conditions of patients in these two groups were statistically analyzed and compared. The Oswestry Disability Index (ODI) scores, Visual Analog Scale (VAS) scores, and sacrospinalis muscle damage evaluation indicators before operation and 3, 12 months postoperation were compared. RESULTS: A total of 31 and 35 cases in the single incision and double incision groups, respectively, completed at least 12 months of systemic follow-up. The differences in perioperative conditions between the two groups were not statistically significant. The incision length of the single incision group was significantly shorter than that of the double incision group (P < 0.01). The ODI and VAS scores of patients in both groups improved significantly at 3 and 12 months postoperation. However, these two indicators at 3 and 12 months postoperation and the sacrospinalis muscle damage evaluation indicators at 3 months postoperation did not differ significantly between the two groups (P ≥ 0.05). CONCLUSIONS: Mast Quadrant-assisted modified TLIF with a small single posterior median incision has excellent clinical feasibility compared to minimally invasive TLIF with a double paramedian incision.

Electrophysiological differences between Hirayama disease, amyotrophic lateral sclerosis and cervical spondylotic amyotrophy.

BACKGROUND: Hirayama disease (HD), amyotrophic lateral sclerosis (ALS) or cervical spondylotic amyotrophy (CSA) may result in atrophy of intrinsic hand and forearm muscles. The incidence of HD is low, and it is rarely encountered in the clinical setting. Consequently, HD is often misdiagnosed as ALS or CSA. It is important to differentiate these diseases because HD is caused by a benign focal lesion that is limited to the upper limbs. METHODS: The thenar and hypothenar compound muscle action potential (CMAP) amplitude of the upper limbs of 100 HD, 97 ALS and 32 CSA cases were reviewed; 35 healthy individuals were included as controls. Seventy-eight percent, 38% and 69% of patients with HD, ALS or CSA had unilateral involvement; the remaining patients were affected bilaterally. Thenar and hypothenar CMAP amplitude evoked by ulnar stimulation was compared with CMAP evoked by median stimulation. RESULTS: The ulnar/median CMAP ratio was found to be lower in HD (0.55 ± 0.41, P<0.0001), higher in ALS (2.28 ± 1.15, P<0.0001) and no different in CSA (1.21 ± 0.53, P>0.05) compared with the normal range from previous studies (0.89-1.60) and with the healthy controls (1.15 ± 0.23). Conduction velocities of the sensory and motor nerves, the amplitude of the sensory nerve action potential, and the CMAP amplitude of the unaffected limb were all normal. CONCLUSIONS: The hand muscles were differentially affected between patients with HD, ALS and CSA. The ulnar/median CMAP ratio could be used to distinguish these three diseases.

Magnetic resonance neurography in analysis of operative safety of transforaminal lumbar interbody fusion in Chinese subjects.

OBJECTIVE: To measure relevant anatomical variables of lumbosacral nerve root and adjacent structures by magnetic resonance neurography (MRN) and analyze operative safety of transforaminal lumbar interbody fusion (TLIF) in Chinese subjects. METHODS: Twelve normal healthy volunteers (six men, six women) underwent MRN of lumbosacral nerve roots at 3.0 T. Three-dimensional imaging was reconstructed with Osirix software and the following anatomic variables measured: (i) distance between nerve root and upper pedicle; (ii) distance between nerve root and lower pedicle; (iii) angle between nerve root and sagittal plane; (iv) distance between upper and lower nerve roots; and (v) distance between upper and lower pedicles. RESULTS: Good images of the L(1)-L(5) nerve roots were obtained by MRN technology in all 12 volunteers. The distance between nerve root and upper pedicle and the angle between nerve roots and the sagittal plane gradually diminished from L(1) to L(5). However, there were no significant variations in the distance between nerve root and lower pedicle or between upper and lower pedicles. From L(1 -2) to L(4 -5), the distances between upper and lower pedicles, which are closely related to the operating space for TLIF in Chinese men and women, were less than 10 mm in most subjects and were significantly smaller in women than in men. The variables did not differ significantly between the left and right sides of the same segment. CONCLUSION: Based on the above anatomical study and measurement analysis, we believe that TLIF puts the upper nerve root at risk in some Chinese patients. However, this conclusion requires confirmation by anatomical study of large samples and clinical validation.

Potential advantages of the H-reflex of the biceps femoris-long head in documenting S1 radiculopathy.

PURPOSE: A novel H-reflex method using the biceps femoris-long head (BF-LH) was investigated to collect the normative data for this reflex arc and assess its clinical utility for S1 radiculopathy evaluation. Comparability with conventional tibial and Sol H-reflex findings was also determined. METHODS: BF-LH H-reflexes were recorded using surface electrodes to S1-root stimulation in 43 unilateral S1 radiculopathy patients (radiculopathy group) and 34 normal subjects (control group) from March 2009 to December 2011. H-M interval and peak-to-peak amplitudes were measured. The BF-LH H-reflex and the H-reflex from the soleus muscle (Sol H-reflex) to both tibial nerve stimulation (tibial H-reflex) and S1-root stimulation were used and compared for application in S1 radiculopathy evaluation. RESULTS: BF-LH H-reflexes were reliably recorded for all control group subjects. Abnormal BF-LH H-reflexes were recorded for 40 (93.0%) radiculopathy group patients in the involved extremity, and abnormal involved side tibial H-reflexes and Sol H-reflexes were recorded in 31 (72.1%) and 41 (95.3%) radiculopathy group patients, respectively. The BF-LH H-reflex exhibited significantly higher sensitivity for evaluation of S1 radiculopathy, accurate in 40 (93.0%) radiculopathy group patients, than that provided by the conventional tibial H-reflex of only 31 (72.1%) (P < 0.05). CONCLUSIONS: The BF-LH H-reflex is a highly sensitive and reliable clinical tool for evaluation of the S1 spinal reflex pathway in radiculopathy that is distinct from the Sol H-reflex and conventional tibial H-reflex arcs.

Effect of rat brain tissue extracts on osteoblast proliferation and differentiation.

PURPOSE: The reason for enhanced fracture healing in traumatic brain injury patients is not clearly understood. It is possible that factors inherent in the brain passing through the blood-brain barrier to the peripheral circulation, or a disruption of central nervous system (CNS) control of the sympathetic nervous system (SNS), stimulates the process of fracture healing. METHODS: In this study, we assessed proliferation [using the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay] and differentiation [using alkaline phosphatase (ALP)] in rat osteoblasts incubated with gray matter or other tissue extracts with and without the addition of an α- or ß-adrenergic receptor blocker (phentolamine or propranolol). RESULTS: Gray matter extract from normal brain caused a dose-dependent increase in osteoblast proliferation and differentiation. Serum from normal rats enhanced differentiation but not proliferation. Alpha-receptor blockade had no effect on proliferation or differentiation. Beta-receptor blockade caused a partial, but statistically significant, decrease in gray matter stimulation of osteoblast differentiation. CONCLUSION: The results of this study indicate that gray matter extract from normal brain increases osteoblast proliferation and differentiation and that ß receptors may be involved in differentiation under these conditions.

Minimally invasive lumbar interbody fusion via MAST Quadrant retractor versus open surgery: a prospective randomized clinical trial.

BACKGROUND: In recent years, a variety of minimally invasive lumbar surgery techniques have achieved desirable efficacy, but some dispute remains regarding the advantages over open surgery. This study aimed to compare minimally invasive lumbar interbody fusion via MAST Quadrant retractor with open surgery in terms of perioperative factors, postoperative back muscle function, and 24-month postoperative follow-up results. METHODS: From September 2006 to June 2008, patients with single-level degenerative lumbar spine disease who were not responsive to conservative treatment were enrolled in this study. Patients were randomized to undergo either minimally invasive surgery (MIS, transforaminal lumbar interbody fusion via MAST Quadrant retractor, 41 cases) or open surgery (improved transforaminal lumbar interbody fusion, 38 cases). RESULTS: The MIS group had longer intraoperative fluoroscopy time than the open surgery group, and the open surgery group had significantly increased postoperative drainage volume and significantly prolonged postoperative recovery time compared with the MIS group (P < 0.05 for all). MRI scanning showed that the T2 relaxation time in the multifidus muscle was significantly shorter in the MIS group than in the open surgery group at 3 months after surgery (P < 0.01). Surface electromyography of the sacrospinalis muscle showed that the average discharge amplitude and frequency were significantly higher in the MIS group than in the open surgery group (P < 0.01). The Oswestry disability index and visual analog scale scores were better at 3, 6, 12 and 24 months postoperatively than preoperatively in both groups. Both groups of patients met the imaging convergence criteria at the last follow-up. CONCLUSIONS: MIS can effectively reduce sacrospinalis muscle injury compared with open surgery, which is conducive to early functional recovery. In the short term, MIS is superior to open surgery, but in the long term there is no significant difference between the two procedures.

[The anatomic study and clinical significance of the modified transforaminal lumbar interbody fusion].

OBJECTIVE: To put some improvements to the traditional transforaminal lumbar interbody fusion (TLIF) and discuss its clinical significance. METHODS: Completed the traditional posterior lumbar interbody fusion (PLIF) and TLIF procedure in 12 fresh cadavers, dissect further to expose the surrounding anatomical structures, and put the modified TLIF surgery according to the anatomical findings. And simulated the operation in 12 fresh cadavers, analyzed its feasibility and potential advantages. RESULTS: The early anatomical study found that the related nerve root was in a state of high tension and certain risk of injury when completed the traditional PLIF and TLIF surgery, and found certain operational area between the superior articular process and the midline structures of the spinous processes and interspinous ligaments. Put the modified TLIF surgical approach according to the anatomical findings, which the operating area is located in PLIF outside and TLIF inside. As the following words: Take a posterior-middle incision, preserve the supraspinous and interspinous ligaments, and the spinous processes, dissect the bilateral paravertebral muscle, expose lamina and facet joints, not including transverse process, and remove unilateral inferior two third lamina, inferior articular process and expose the articular surface of the superior articular process, then dispose the intervertebral space for interbody fusion obliquely in the unilateral approach. Successfully completed the modified TLIF procedure in 12 fresh cadavers, the results showed that the technique has the following advantages. (1) Only remove unilateral inferior two third lamina and inferior articular process, preserve the supraspinous and interspinous ligaments, and the spinous processes, not expose the transverse process. (2) Both central canal, and lateral recess and nerve root canal of the operative side can be decompressed effectively simultaneously. (3) Avoid excessive traction to the thecal sac and traversing nerve roots and decrease the injury rate due to the reservation of the midline structures and the oblique manipulation, and less injury rate of the exiting nerve root, because of not necessary to expose it routinely. CONCLUSIONS: The modified TLIF is safe and feasible, could effectively reduce the nerve roots injuries. Maybe it's a better choice for most of the Chinese patients at present.