Masateru Nagae

Platelet-rich plasma enhances the initial mobilization of circulation-derived cells for tendon healing.

Circulation‐derived cells play a crucial role in the healing processes of tissue. In early phases of tendon healing processes, circulation‐derived cells temporarily exist in the wounded area to initiate the healing process and decrease in number with time. We assumed that a delay of time‐dependent decrease in circulation‐derived cells could improve the healing of tendons. In this study, we injected platelet‐rich plasma (PRP) containing various kinds of growth factors into the wounded area of the patellar tendon, and compared the effects on activation of circulation‐derived cells and enhancement of tendon healing with a control group (no PRP injection). To follow the circulation‐derived cells, we used a green fluorescent protein (GFP) chimeric rat expressing GFP in the circulating cells and bone marrow cells. In the PRP group, the numbers of GFP‐positive cells and heat‐shock protein (HSP47; collagen‐specific molecular chaperone)‐positive cells were significantly higher than in the control group at 3 and 7 days after injury. At the same time, the immunoreactivity for types I and III collagen was higher in the PRP group than in the control group at early phase of tendon healing. These findings suggest that locally injected PRP is useful as an activator of circulation‐derived cells for enhancement of the initial tendon healing process. J. Cell. Physiol. 215: 837–845, 2008.

In vivo evaluation of rabbit sciatic nerve regeneration with diffusion tensor imaging (DTI): correlations with histology and behavior

Diffusion tensor imaging (DTI) is widely used in the study of the central nervous system. DTI represents a potential diagnostic tool for the peripheral nerve. However, more detailed information is needed for application of DTI in the clinical setting. In this study, peripheral degeneration and regeneration were evaluated using DTI-based analyses in a rabbit model. The changes in DTI parameters were compared to histological and functional changes after nerve injury. We used a high magnetic field (7.04T) MRI system. Japanese white male rabbits were used as the model of sciatic nerve crush injury. MR images were obtained before injury and at 2, 4, 6 and 8 weeks post-injury. The DTI parameters of fractional anisotropy (FA), axial diffusivity (λ||), and radial diffusivity (λ⊥) were calculated. Our results showed decreased FA and increased λ⊥ during the degenerative phase after sciatic nerve injury. In contrast, increased FA and decreased λ⊥ were observed during the regenerative phase. FA changes were correlated with axon number and with motor function recovery, assessed with the toe-spreading index. This study clearly demonstrates the validity of applying DTI parameters to the in vivo evaluation of peripheral nerve regeneration. Furthermore, results suggest that DTI can be a potent tool for predicting the extent of functional recovery after peripheral nerve injury.

Hepatocyte growth factor/c-met promotes proliferation, suppresses apoptosis, and improves matrix metabolism in rabbit nucleus pulposus cells in vitro

The etiology of intervertebral disc (IVD) degeneration is closely related to apoptosis and extracellular matrix degradation in nucleus pulposus (NP) cells. These defects in NP cells are induced by excessive external stressors such as reactive oxygen species (ROS) and inflammatory cytokines. Recently, hepatocyte growth factor (HGF) has been shown to repair damage in various diseases through anti‐apoptotic and anti‐inflammatory activity. In this study, we investigated the effects of HGF on NP cell abnormality caused by ROS and inflammatory cytokines by using primary NP cells isolated from rabbit IVD. HGF significantly enhanced the proliferation of NP cells. Apoptosis of NP cells induced by H2O2 or TNF‐α was significantly inhibited by HGF. Induction of mRNA expression of the inflammation mediators cyclooxygenase‐2 and matrix metalloproteinase‐3 and ‐9 by TNF‐α was significantly suppressed by HGF treatment. Expression of c‐Met, a specific receptor for HGF, was confirmed in NP cells and was increased by TNF‐α, suggesting that inflammatory cytokines increase sensitivity to HGF. These findings demonstrate that activation of HGF/c‐Met signaling suppresses damage caused by ROS and inflammation in NP cells through multiple pathways. We further suggest the clinical potential of HGF for counteracting IVD degradation involved in NP cell abnormalities.

Effects of stress-shielding on the dynamic viscoelasticity and ordering of the collagen fibers in rabbit Achilles tendon.

We investigated the effects of stress‐shielding on both viscoelastic properties and microstructure of collagen fibers in the Achilles tendon by proton double‐quantum filtered (1H‐DQF) NMR spectroscopy. The right hind‐limbs of 20 Japanese white rabbits were immobilized for 4 weeks in a cast with the ankle in plantarflexion. Dynamic viscoelasticity of the Achilles tendons was measured using a viscoelastic spectrometer. Proton DQF NMR signals were analyzed to determine the residual dipolar coupling of bound water molecules in the Achilles tendons. Both the dynamic storage modulus (E′) and dynamic loss modulus (E″) decreased significantly in the Achilles tendons of the stress‐shielding group. The results of the 1H‐DQF NMR examination demonstrated significantly reduced residual dipolar coupling in the Achilles tendons of this same group. The disorientation of collagen fibers by stress‐shielding should contribute to degradation of the dynamic storage and loss moduli. The alterations of the collagen fiber orientation that contributed to the function of tendinous tissue can be evaluated by performing an analysis of 1H DQF NMR spectroscopy.

Prevention of neurological complications using a neural monitoring system with a finger electrode in the extreme lateral interbody fusion approach

OBJECTIVE Extreme lateral interbody fusion (XLIF) is a minimally disruptive surgical procedure that uses a lateral approach. There is, however, concern about the development of neurological complications when this approach is used, particularly at the L4-5 level. The authors performed a prospective study of the effects of a new neural monitoring system using a finger electrode to prevent neurological complications in patients treated with XLIF and compared the results to results obtained in historical controls. METHODS The study group comprised 36 patients (12 male and 24 female) who underwent XLIF for lumbar spine degenerative spondylolisthesis or lumbar spine degenerative scoliosis at L4-5 or a lower level. Using preoperative axial MR images obtained at the mid-height of the disc at the treated level, we calculated the psoas position value (PP%) by dividing the distance from the posterior border of the vertebral disc to the posterior border of the psoas major muscle by the anteroposterior diameter of the vertebral disc. During the operation, the psoas major muscle was dissected using an index finger fitted with a finger electrode, and threshold values of the dilator were recorded before and after dissection. Eighteen cases in which patients had undergone the same procedure for the same indications but without use of the finger electrode served as historical controls. Baseline clinical and demographic characteristics, PP values, clinical results, and neurological complications were compared between the 2 groups. RESULTS The mean PP% values in the control and finger electrode groups were 17.5% and 20.1%, respectively (no significant difference). However, 6 patients in the finger electrode group had a rising psoas sign with PP% values of 50% or higher. The mean threshold value before dissection in the finger electrode group was 13.1 ± 5.9 mA, and this was significantly increased to 19.0 ± 1.5 mA after dissection (p < 0.001). A strong negative correlation was found between PP% and threshold values before dissection, but there was no correlation with threshold values after dissection. The thresholds after dissection improved to 11 mA or higher in all patients. There were no serious neurological complications in any patient, but there was a significantly lower incidence of transient neurological symptoms in the finger electrode group (7 [38%] of 18 cases vs 5 [14%] of 36 cases, p = 0.047). CONCLUSIONS The new neural monitoring system using a finger electrode may be useful to prevent XLIF-induced neurological complications.

Evaluation of resorption and biocompatibility of collagen hemostats in the spinal epidural space

BACKGROUND CONTEXT Collagen hemostats have different characteristics depending on their properties and configuration. In vivo serial evaluation of local reactions because of placement of hemostats in the epidural space has not been reported. PURPOSE This study compared the resorption and biocompatibility of two types of collagen hemostats placed in the epidural space. STUDY DESIGN This in vivo study used experimental animals to evaluate collagen hemostats that were placed in the epidural space. METHODS A ligamentum flavum resection model was created in Japanese white rabbits (n=65). A microfibrillar collagen hemostat (MCH group, n=5), cotton-type collagen hemostat (CCH group, n=5) that was chemically cross-linked, or no hemostat (control group, n=4) was placed in the spinal epidural space. For histologic evaluation, each group was euthanized 1, 2, 4, and 8 weeks postoperatively (PO), and hematoxylin-eosin and immunohistochemical (IHC) staining for inflammatory cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-6), cyclooxygenase (COX)-2, and macrophages (CD68) was performed. To evaluate exudate accumulation and the degree of inflammation in the epidural space, magnetic resonance imaging at 7.04 T was serially performed in each group (n=3) under anesthesia and sedation. RESULTS The collagen hemostats in both groups were reabsorbed at 4 weeks PO. In the MCH group, there was inflammatory cell infiltration and granuloma formation around the hemostat, TNF-α-positive cells were seen up to 1 week, and IL-6-, COX-2-, and CD68-positive cells were seen at all evaluation times. In the CCH group, no inflammatory cell infiltration around the hemostat was observed, and IHC staining showed no positive cells at 4 weeks PO and later. T2*-weighted MR images showed significantly higher mean signal intensity of the epidural space in the MCH group than in the CCH group but only at 1 week PO (p<.05). CONCLUSIONS Resorption of both hemostats was similar. In the MCH group, there was intense tissue inflammation around the hemostatic material, and MR images showed high signal intensity because of exudate accumulation in the epidural space. This indicated a strong foreign-body reaction to the MCH, thus demonstrating a difference in biocompatibility with the CCH.

Magnetic Resonance Imaging Evaluation of the Effects of Surgical Invasiveness on Paravertebral Muscles Following Muscle-preserving Interlaminar Decompression (MILD).

Study Design: This is a retrospective study. Objectives: The aim of this study was to determine the extent of damage to the paravertebral muscles after muscle-preserving interlaminar decompression (MILD) using magnetic resonance imaging to evaluate changes in the multifidus muscle (MF). Summary of Background Data: Short-term surgical outcomes of MILD for lumbar spinal canal stenosis (LSCS) are satisfactory; however, the extent of damage to the paravertebral muscles after MILD remains unclear. Methods: Thirty-four patients (18 men/16 women; mean age: 72.6 y) who had LSCS treated with MILD were retrospectively investigated. A total of 61 decompressed disk levels [L2/3(5); L3/4(21); L4/5(30); L5/S(5)] and 34 nondecompressed levels (L1/2) were assessed. There was 1 decompressed disk level in 12 cases, 2 in 17 cases, and 3 in 5 cases. Magnetic resonance imaging scans were obtained before surgery and at 3 and 12–18 months after surgery, using the same scanner. The rate of paravertebral muscle atrophy was evaluated to compare the area of the MF in the T2-weighted axial plane (intervertebral disk level) preoperatively and postoperatively, using OsiriX Medical Imaging Software. Changes in muscle signal intensity were also recorded. Statistical analysis was performed using 3-way analysis of variance with the post hoc Fisher PSLD test. Results: The rate of MF atrophy was 4.0% at the decompressed levels and 2.1% at the nondecompressed levels. There were no changes of signal intensity in the MF between the preoperative and postoperative periods. In decompressed levels, muscle atrophy and signal intensity were significantly improved from 3 months to 12–18 months after surgery. The number and level of the decompressed disks did not affect the extent of muscle injury. Conclusions: The extent of paravertebral muscle injury after MILD is satisfactory. The midline interlaminar approach used in this technique may prevent local denervation and irreversible damage to the paravertebral muscles. These results indicate that MILD is useful to treat LSCS less invasively.

Innovative Technique for the Placement of the Drainage Tube for Microendoscopic Spinal Decompression.

Study Design: A technical note and retrospective study. Objectives: The objectives were to describe a new method of drainage tube placement during microendoscopic spinal decompression, and compare the positioning and fluid discharge obtained with this method and the conventional method. Summary of Background Data: To prevent postoperative epidural hematoma after microendoscopic decompression, a drainage tube must be placed in a suitable location. However, the narrow operative field makes precise control of the position of the tube technically difficult. We developed a method to reliably place the tube in the desired location. Materials and Methods: We use a Deschamps aneurysm needle with a slightly curved tip, which we call a drain passer. With the microendoscope in position, the drain passer, with a silk thread passed through the eye at the needle tip, is inserted percutaneously into the endoscopic field of view. The drainage tube is passed through the loop of silk thread protruding from the inside of the tubular retractor, and the thread is pulled to the outside, guiding the end of the drainage tube into the wound. This method was used in 23 cases at 44 intervertebral levels (drain passer group), and the conventional method in 20 cases at 32 intervertebral levels (conventional group). Postoperative plain radiographs were taken, and the amount of fluid discharge at postoperative hour 24 was measured. Results: Drainage tube positioning was favorable at 43 intervertebral levels (97.7%) in the drain passer group and 26 intervertebral levels (81.3%) in the conventional group. Mean fluid discharge was 58.4±32.2 g in the drain passer group and 38.4±23.0 g in the conventional group. Positioning was significantly better and fluid discharge was significantly greater in the drain passer group. Conclusion: The results indicate that this method is a useful drainage tube placement technique for preventing postoperative epidural hematoma.

Clinical Outcome of Muscle-Preserving Interlaminar Decompression (MILD) for Lumbar Spinal Canal Stenosis: Minimum 5-Year Follow-up study

Introduction Favorable short-term outcomes have been reported following muscle-preserving interlaminar decompression (MILD), a less invasive decompression surgery for lumbar spinal canal stenosis (LSCS). However, there are no reports of mid- to long-term outcomes. The purpose of this study was to evaluate the clinical outcomes five or more years after treatment of LSCS with MILD. Methods Subjects were 84 cases with LSCS (44 males; mean age, 68.7 years) examined five or more years after MILD. All patients had leg pain symptoms, with claudication and/or radicular pain. The patients were divided into three groups depending on the spinal deformity: 44 cases were without deformity (N group); 20 had degenerative spondylolisthesis (DS group); and 20 had degenerative scoliosis (DLS group). The clinical evaluation was performed using Japanese Orthopedic Association (JOA) scores, and revision surgeries were examined. Changes in lumbar alignment and stability were evaluated using plain radiographs. Results The overall JOA score recovery rate was 65.5% at final follow-up. The recovery rate was 69.5% in the N group, 65.2% in the DS group, and 54.0% in the DLS group, with the rate of the DLS group being significantly lower. There were 16 revision surgery cases (19.0%): seven in the N group (15.9%), three in the DS group (15.0%) and six in the DLS group (30.0%). There were no significant differences between pre- and postoperative total lumbar alignment or dynamic intervertebral angle in any of the groups, slip percentage in the DS group, or Cobb angle in the DLS group. Conclusions The mid-term clinical results of MILD were satisfactory, including in cases with deformity, and there was no major impact on radiologic lumbar alignment or stability. The clinical outcomes of cases with degenerative scoliosis were significantly less favorable and the revision rate was high. This should be taken into consideration when deciding on the surgical procedure.

Effect of three-dimensional rotational deformity correction in surgery for adult degenerative scoliosis using lumbar lateral interbody fusion and posterior pedicle screw fixation

Introduction Corrective surgery for adult degenerative scoliosis using lateral interbody fusion (LIF) and additional posterior fixation is an efficient procedure. However, it is unclear how this procedure affects rotational deformity correction. Therefore, the goal of the present study was to use three-dimensional (3D) images, taken during surgery, to investigate rotational deformity correction in the treatment of adult degenerative scoliosis using LIF and posterior fixation using a pedicle screw system. Methods The subjects were 12 females who were treated using LIF and posterior fixation for adult degenerative scoliosis. The patients had a mean age of 72 (65-76) years. 3D images were acquired before surgery, after LIF, and after additional posterior fixation. Rotational angles of the upper vertebra with respect to the lower vertebra of each fixed segment were measured in 3 planes. Correction factors for rotational deformity were investigated after LIF and additional posterior fixation. Results There were significant improvements in radiographical parameters for global spinal balance. The correction angles per segment were 4.7° for lateral bending, 6.9° for lordosis, and 4.5° for axial rotation. LIF was responsible for correction of four-fifths of lateral bending and axial rotation, and two-thirds of lordotic changes. Conclusions Lateral bending, axial rotational deformities, and lordosis were primarily corrected by LIF. Further lordosis correction was achieved using additional posterior fixation. These results indicate that corrective surgery for adult degenerative scoliosis using these procedures is effective for rotational deformity correction and leads to an ideal global spinal alignment.