Validity of two-dimensional analysis using a tablet computer for estimation of foot arch height during walking.

[Purpose] To examine the validity of two-dimensional analysis using a tablet computer for the estimation of arch height during walking by comparing it with a motion capture system and static foot alignment screenings. [Participants and Methods] Fourteen healthy males and 15 healthy females participated in this study. The arch height of the right foot while walking was simultaneously measured using a tablet computer and motion capture system. Dynamic foot alignment, including arch height, at the mid-stance and pre-swing phases was calculated from the kinematic data measured using the tablet computer and motion analysis system. Static foot alignment was also assessed by screening tests including arch height index and foot posture index. [Results] Arch height measured using a tablet computer showed a significant high correlation with that measured using the motion capture system at the mid-stance and pre-swing phases. Arch height index showed a significant moderate correlation with arch height measured using the motion capture system at the mid-stance phase. Meanwhile, foot posture index showed no relationship with arch height measured by the motion capture system. [Conclusion] These results demonstrate the high validity of dynamic foot analysis using a tablet computer for the estimation of arch height during walking. Such gait analysis can be effective for assessing dynamic foot alignment in clinical practice.

Japanese 2011 nationwide survey on complications from spine surgery.

BACKGROUND: The Japanese Society for Spine Surgery and Related Research (JSSR) previously carried out two nationwide surveys in 1994 and 2001 on complications from spine and spinal cord surgery. More than 10 years have now elapsed since 2001. Rapidly ageing populations have major impacts on society, particularly in the medical field. The purpose of this study was therefore to examine the present situation for spine surgery in Japan. METHODS: The JSSR research team prepared a computerized questionnaire made up of two categories in order to capture clinicopathological information and surgical information. A recordable optical disc for data storage was sent to surgeons who were certified for spine surgery by JSSR. The data was analyzed. RESULTS: The JSSR carried out a nationwide survey of complications of 31,380 patients. Patients aged 60 years or older comprised 63.1 % of the overall cohort. This was considerably higher than observed in previous surveys. Degenerative spinal diseases increased 79.7 %. With regard to surgical approach, the incidence of anterior surgery has decreased, while that of posterior surgery has increased compared to the earlier surveys (both p < 0.05). Spinal instrumentation was applied in 30.2 % cases, compared to 27.0 and 34.0 % cases in the 1994 and 2001 surveys, respectively. Intraoperative and postoperative complications were reported in 10.4 % and were slightly increased compared to 8.6 % in the earlier surveys (both p < 0.05). Diseases associated with a high incidence of complication included intramedullary tumor (29.3 %) and primary malignant tumor (22.0 %). The highest incidence of complication was dural tear (2.1 %), followed by neurological complication (1.4 %).

The Effects of a Lateral Wedge Insole on Knee and Ankle Joints During Slope Walking.

The purpose of this study was to determine whether a lateral wedge insole reduces the external knee adduction moment during slope walking. Twenty young, healthy subjects participated in this study. Subjects walked up and down a slope using 2 different insoles: a control flat insole and a 7° lateral wedge insole. A three-dimensional motion analysis system and force plate were used to examine the knee adduction moment, the ankle valgus moment, and the moment arm of the ground reaction force to the knee joint center in the frontal plane. The lateral wedge insole significantly decreased the moment arm of the ground reaction force, resulting in a reduction of the knee adduction moment during slope walking, similar to level walking. The reduction ratio of knee adduction moment by the lateral wedge insole during the early stance of up-slope walking was larger than that of level walking. Conversely, the lateral wedge insole increased the ankle valgus moment during slope walking, especially during the early stance phase of up-slope walking. Clinicians should examine the utilization of a lateral wedge insole for knee osteoarthritis patients who perform inclined walking during daily activity, in consideration of the load on the ankle joint.

Combined posterior and delayed staged mini-open anterior short-segment fusion for thoracolumbar burst fractures.

STUDY DESIGN: A prospective study. OBJECTIVES: To assess the outcome of patients with a single thoracolumbar burst fracture treated with circumferential short-segment fusion consisting of posterior reduction, short-segment fusion, and delayed staged mini-open anterior short-segment fusion. SUMMARY OF BACKGROUND DATA: The surgical treatment of thoracolumbar burst fractures remains controversial. In attempting to combine the advantages of posterior procedures, including initial correction of kyphosis and early decompression, and those of anterior procedures, including direct decompression and restoration of anterior column support, a combined posterior and delayed staged anterior procedure seems to be a reasonable choice. However, conventional combined procedures are invasive. METHODS: We prospectively selected 28 consecutive patients with single thoracolumbar burst fracture for circumferential short-segment fusion consisting of posterior reduction, short-segment fusion, and delayed staged mini-open anterior short-segment fusion. The pedicle screw systems were removed after confirmation of posterior bony fusion to preserve as many motion segments as possible in those patients who could be treated with circumferential monosegmental fusion. Radiographic and clinical assessment of 28 patients who received this treatment was carried out. RESULTS: The mean loss of correction of kyphosis between the time of the combined procedure and final follow-up was 3.7 degrees (range, 0 to 10.2 degrees). Bony fusion was eventually achieved in all patients. There were 15 cases with monosegmental and 13 cases with bisegmental circumferential fusion. All 10 patients with initial neurological deficit improved by at least 1 Frankel grade: 3 improved by 1 grade, 5 improved by 2 grades, and 2 improved by 3 grades. In total, 27 patients, who were P1 or P2 on the Denis pain scale, were considered to have obtained clinically satisfactory results. CONCLUSIONS: This combined procedure is less invasive than the conventional combined one, and finally achieves shorter stabilization, resulting in preservation of motion segments. It thus seems to be a reasonable treatment option for thoracolumbar burst fractures.

Surgical results of the resection of spinal meningioma with the inner layer of dura more than 10 years after surgery.

Most spinal meningiomas arise from the thoracic dura in middle-aged and elderly women. Simpson grade 1 resection is recommended to avoid recurrence. For ventral and ventrolateral tumors, reconstruction after total dural resection is difficult, and spinal fluid leakage is likely. To overcome this concern, Saito et al. developed the technique of resecting the tumor with the inner dural layer, preserving the outer dural layer. Although meningioma rarely recurs, the recurrence period is approximately 8 years postoperatively. No studies have evaluated long-term (> 10-year) outcomes of the Saito method. Here, we report 10 cases of the Saito method with > 10-year follow-up and compare outcomes with those of other standard approaches. Twenty-nine pathology-confirmed meningioma patients underwent surgery in our department, ten with the Saito method. We investigated resection method (dura mater treatment), pathological type, and recurrence and compared pre- and postoperative clinical findings. The median follow-up was 132 months. Recurrence occurred after Simpson grades 3 and 4 resection. Simpson grades 1, 2, and the Saito method resulted in no recurrence. Neurological symptoms improved in all patients at final follow-up. This is the first report of long-term outcomes of the Saito method. The method achieved good neurological improvement with no recurrence in > 10-year follow-up.

Intradural neurenteric cyst--two case reports of surgical treatment.

Intradural neurenteric cysts are rare congenital lesions and arise from incomplete separation of the developing notochord and foregut in the embryo. Neurenteric cysts are often seen in conjunction with other forms of occult spinal dysraphism. The cases of a 48-year-old male with pain in the right shoulder and numbness in both hands and a 7-year-old girl with subacute muscle weakness of the lower extremities are presented. Both patients underwent surgery. One lesion was completely excised, while the other could be only partially removed because of negative monitoring potential during the operation. Histological examination, showing pseudostratified ciliated columnar epithelium, confirmed the diagnosis of neurenteric cyst. The symptoms in both patients nearly disappeared after surgery. Recurrence of cyst was observed in the girl, though without neurological symptoms. In conclusion, two cases of intradural extramedullary cysts are reported. Clinical presentations, intraoperative findings, and histological features are discussed with a review of the literature.

L2-L3 flexion-distraction injury treated by posterior fusion using ultra-high molecular weight polyethylene tape in a 7-year-old boy.

A 7-year-old boy was sitting in the back seat of a car wearing a lap seatbelt when the car was involved in a head-on collision with another vehicle. Radiographs revealed mild scoliosis, anterior column compression of L3 and enlargement of both the intervertebral foramen and interspinous distance between L2 and L3. Computed tomography revealed bilateral L2-L3 facet joint disruption with fracture of the L2 spinous process. Magnetic resonance imaging revealed rupture of the posterior ligamentous complex. An open reduction and posterior fusion with autologous bone graft using 5-mm-wide ultra-high molecular weight polyethylene tape sublaminar wiring was performed. Three months after surgery, bony fusion of L2-L3 was observed. At 6 months after surgery, the patient was asymptomatic and had resumed previous activities.

Effectiveness of simple tracing test as an objective evaluation of hand dexterity.

This study aimed to demonstrate that the simple tracing test (STT) is useful for assessing the hand dexterity in patients with cervical spondylotic myelopathy (CSM) by comparing STT scores between healthy volunteers and CSM patients. This study included 25 CSM patients and 38 healthy volunteers. In the STT, the participants traced a sine wave displayed on a tablet device at a comfortable pace, and the tracing accuracy, changes in the total sum of pen pressures, and tracing duration were assessed. Data were analyzed using an artificial neural networks (ANN) model to obtain STT scores. All participants were evaluated using the subsection for the upper extremity function of the Japanese Orthopaedic Association (JOA) scoring system for cervical myelopathy (JOA subscore for upper extremity function) and the grip and release test (GRT). The results were compared with the STT scores. The mean STT scores were 24.4 ± 32.8 in the CSM patients and 84.9 ± 31.3 in the healthy volunteers, showing a significant difference. The STT scores showed highly positive correlations with both the JOA subscore for upper extremity function (r = 0.66; P < 0.001) and GRT values (r = 0.74; P < 0.001). Furthermore, receiver operating characteristic analysis showed an area under the curve of 0.89 (95% confidence interval, 0.76-1.00), demonstrating that STT has excellent discriminative ability. This study revealed that STT enables accurate assessment of the hand dexterity in CSM patients.

Validity of Measurement for Trailing Limb Angle and Propulsion Force during Gait Using a Magnetic Inertial Measurement Unit.

Propulsion force and trailing limb angle (TLA) are meaningful indicators for evaluating quality of gait. This study examined the validity of measurement for TLA and propulsion force during various gait conditions using magnetic inertial measurement units (IMU), based on measurements using a three-dimensional motion analysis system and a force platform. Eighteen healthy males (mean age 25.2 ± 3.2 years, body height 1.70 ± 0.06 m) walked with and without trunk fluctuation at preferred, slow, and fast velocities. IMU were fixed on the thorax, lumbar spine, and right thigh and shank. IMU calculated the acceleration and tilt angles in a global coordinate system. TLA, consisting of a line connecting the hip joint with the ankle joint, and the laboratory's vertical axis at late stance in the sagittal plane, was calculated from thigh and shank segment angles obtained by IMU, and coordinate data from the motion analysis system. Propulsion force was estimated by the increment of velocity calculated from anterior acceleration measured by IMU fixed on the thorax and lumbar spine, and normalized impulse of the anterior component of ground reaction force (AGRF) during late stance. Similarity of TLA measured by IMU and the motion analysis system was tested by the coefficient of multiple correlation (CMC), intraclass correlation coefficient (ICC), and root mean square (RMS) of measurement error. Relationships between normalized impulse of AGRF and increments of velocity, as measured by IMU, were tested using correlation analysis. CMC of TLA was 0.956-0.959. ICC between peak TLAs was 0.831-0.876 (p < 0.001), and RMS of error was 1.42°-1.92°. Velocity increment calculated from acceleration on the lumbar region showed strong correlations with normalized impulse of AGRF (r = 0.755-0.892, p < 0.001). These results indicated a high validity of estimation of TLA and propulsion force by IMU during various gait conditions; these methods would be useful for best clinical practice.

Extraforaminal L5 Nerve Root Compression Caused by Intervertebral Osteophyte Accompanied by Lumbosacral Transitional Vertebra: A Case Treated by Anterior Approach.

BACKGROUND: Several authors have reported the occurrence of extraforaminal L5 nerve root compression between lumbosacral transitional vertebrae (LSTV) and sacral ala, but reports on a lesion caused by an intervertebral osteophyte on the ventral and contralateral side of a unilateral abnormality by LSTV are hardly available. CASE DESCRIPTION: A 67-year-old woman presented with pain along the distribution of the L5 nerve root; straight leg raise test, femoral nerve stretch test, and Kemp test were positive on the left. Following plain radiographs, computerized tomography, magnetic resonance imaging, and selective nerve root block, an osteophyte bridging the L5 and S1 vertebral bodies in the ventral side was identified compressing the L5 nerve root. On account of resistance to conservative therapy and the delicate position of the lesion, surgical treatment was performed by an anterior decompression. Subsequently, the patient attained adequate relief from pain and could walk normally. CONCLUSION: We herein present a very rare case of extraforaminal L5 nerve root compression caused by an intervertebral osteophyte on the ventral and contralateral side of a unilateral abnormality by LSTV, which was managed by anterior decompression.

Biomechanical characterization of slope walking using musculoskeletal model simulation.

PURPOSE: Upslope and downslope walking are basic activities necessary for normal daily living in community, and they impose greater joint load on the lower extremities than during level walking. Thus, the purpose of this study was to quantify the resultant and shear forces in the hip and knee joints during slope walking. METHODS: Twelve healthy volunteers were evaluated when walking under level and 10° up- and downslope conditions. Three-dimensional gait analysis was conducted using a 7-camera optoelectronic motion analysis system combined with a force plate to measure ground reactive force. Joint forces in the hip and knee joints were estimated using musculoskeletal model simulation. RESULTS: Results showed that the resultant hip force was increased significantly to 117.2% and 126.9%, and the resultant knee force was increased to 133.5% and 144.5% in up- and downslope walking, respectively, compared to that of level walking. Furthermore, increased shear force in the hip and knee joints was noted during both slope walking conditions. CONCLUSIONS: This information may be beneficial for therapists advising elderly people or patients with osteoarthrosis on an appropriate gait pattern, gait assistive devices, or orthoses according to their living environment.

Risk Factors for Postoperative Ileus after Scoliosis Surgery.

INTRODUCTION: One complication after scoliosis surgery is ileus; however, few reports have described the frequency of and risk factors for this complication. We conducted a retrospective clinical study with logistic regression analysis to confirm the frequency of and risk factors for ileus after scoliosis surgery. METHODS: After a retrospective review of data from patients who underwent surgical correction of spinal deformity from 2009 to 2014, 110 cases (age range, 4-73 yr; median, 14 yr) were included in the study. We defined postoperative ileus (POI) as a surgical complication characterized by decreased intestinal peristalsis and the absence of stool for more than 3 days postoperatively. Various parameters were compared between patients with POI and those without POI. Logistic regression analysis was performed to assess the risk factors associated with ileus; a P value of <0.05 was considered statistically significant. RESULTS: Fifteen of 110 (13.6%) cases developed POI. The median height, weight, operation time, and blood loss volume of the patients with versus without POI were 146 versus 152 cm, 39.0 versus 44.0 kg, 387 versus 359 min, and 1590 versus 1170 g, respectively. There were no significant differences between patients with versus without POI in the measured parameters, with the exception of patient height, bed rest period, and presence of neuromuscular scoliosis. Multiple logistic regression analysis revealed neuromuscular scoliosis as a significant risk factor for POI (odds ratio, 4.21; 95% CI, 1.23-14.40). CONCLUSIONS: Our findings indicate a high probability of POI after scoliosis surgery, with an incidence of 13.6%. Neurogenic scoliosis, but not lowest instrumented vertebra or correction rate, was a risk factor for POI after scoliosis surgery. Digestive symptoms should be carefully monitored after surgery, particularly in patients with neuromuscular scoliosis.

Prevalence and Location of Neuropathic Pain in Lumbar Spinal Disorders: Analysis of 1804 Consecutive Patients With Primary Lower Back Pain.

STUDY DESIGN: A cross-sectional study of 1804 consecutive patients. OBJECTIVE: The aim of this study was to investigate the prevalence of pathological pain and its distribution features in patients with chronic lumbar spinal disorders. SUMMARY OF BACKGROUND DATA: Clinical spinal disorders can involve pathological neuropathic pain (NeP) as well as physiological nociceptive pain (NocP), as they have varied pathology, including spinal cord injury, stenosis, and compression. A study conducted by the Japanese Society for Spine Surgery and Related Research (JSSR) has determined a prevalence of 29.4% for NeP in patients with lumbar spinal disorder. However, the data did not include information on pain location. METHODS: Patients aged 20 to 79 years with chronic lower back pain (≥3 months, visual analog scale score ≥30) were recruited from 137 JSSR-related institutions. Patient data included an NeP screening questionnaire score and pain location (lower back, buttock, and legs). The association between the pain pathology and its location was analyzed statistically using the unpaired t test and Chi-square test followed by Fisher test. P < 0.05 was considered significant. RESULTS: Low back pain subjects showed 31.9% of NeP prevalence, and the pain distribution showed [NocP(%)/NeP(%)] low back pain only cases: 44/22, while low back pain with leg pain cases showed a prevalence of 56/78. This indicates that low back pain alone can significantly induce NocP rather than NeP (P < 0.01). Buttock pain was revealed to significantly induce both lower back pain and leg pain with NeP properties (P < 0.01). Leg pain was revealed to be predominantly neuropathic, especially when it included peripheral pain (P < 0.01). CONCLUSION: Low back pain with no buttock pain induces NocP rather than NeP. Buttock pain is significantly associated with NeP prevalence whether or not leg pain exists. Leg pain can increase the prevalence of NeP, especially when it contains a peripheral element. LEVEL OF EVIDENCE: 3.

Risk factors for venous thromboembolism after spine surgery.

The efficacy and safety of chemical prophylaxis to prevent the development of deep venous thrombosis (DVT) or pulmonary embolism (PE) following spine surgery are controversial because of the possibility of epidural hematoma formation. Postoperative venous thromboembolism (VTE) after spine surgery occurs at a frequency similar to that seen after joint operations, so it is important to identify the risk factors for VTE formation following spine surgery. We therefore retrospectively studied data from patients who had undergone spinal surgery and developed postoperative VTE to identify those risk factors. We conducted a retrospective clinical study with logistic regression analysis of a group of 80 patients who had undergone spine surgery at our institution from June 2012 to August 2013. All patients had been screened by ultrasonography for DVT in the lower extremities. Parameters of the patients with VTE were compared with those without VTE using the Mann-Whitney U-test and Fisher exact probability test. Logistic regression analysis was used to analyze the risk factors associated with VTE. A value of P < 0.05 was used to denote statistical significance. The prevalence of VTE was 25.0% (20/80 patients). One patient had sensed some incongruity in the chest area, but the vital signs of all patients were stable. VTEs had developed in the pulmonary artery in one patient, in the superficial femoral vein in one patient, in the popliteal vein in two patients, and in the soleal vein in 18 patients. The Mann-Whitney U-test and Fisher exact probability test showed that, except for preoperative walking disability, none of the parameters showed a significant difference between patients with and without VTE. Risk factors identified in the multivariate logistic regression analysis were preoperative walking disability and age. The prevalence of VTE after spine surgery was relatively high. The most important risk factor for developing postoperative VTE was preoperative walking disability. Gait training during the early postoperative period is required to prevent VTE.

Traumatic injury-induced midkine expression in the adult rat spinal cord during the early stage.

Spinal cord injury is a debilitating condition. Midkine (MK) is involved in the generation of the central nervous system during development; however, the role of MK in the mature spinal cord has not been clarified. We examined the expression of MK, which has neurotrophic activity, before and after traumatic injury to the adult rat spinal cord. Following laminectomy, the rat spinal cord was injured at the T-9 level by applying extradural static weight-compression, in which a cylindrical compressor was used to induce complete and irreversible transverse spinal cord injury with paralysis of the lower extremities. The expression of MK was examined up to 14 days after the injury by immunohistochemical and Western blot analyses. Intense MK immunoreactivity was observed in the gray matter around the injury site but not in the necrotic lesion 1-7 days postinjury, although it was slightly positive 14 days after the injury. MK immunoreactivity was not detected in the normal spinal cord. The expression of MK was an early event, and its expression was compared to the increased production of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytes, that was elevated at 2 days postinjury and continued over a 14 day period following the injury. Double immunostaining with anti-MK and anti-GFAP showed the existence of MK in the astrocytic cytoplasm. These findings suggest that MK was produced in astrocytes approximating the damaged region and may represent a reparative neurotrophic factor during the early phase of traumatic injury of the spinal cord.

Changes in nitric oxide and expression of nitric oxide synthase in spinal cord after acute traumatic injury in rats.

The aim of this study was to observe the time course of NO production and NOS expression in the spinal cord following acute traumatic injury. Rat spinal cord was injured by extradural static weight-compression, which resulted in an incomplete transverse spinal cord lesion with paralysis of the lower extremities. Using this model, measurement of NO by microdialysis and Griess reaction and histological and immunohistochemical examinations using polyclonal antibodies to nNOS and iNOS were performed from immediately to 14 days after injury. In injured cord, the amount of NO markedly increased immediately after injury and gradually decreased between 1 and 12 h after injury. A second wave of increase in NO level was observed at 24 h and 3 days after injury. Histologically, hematomas and necrotic changes were observed after injury and demyelination of nerve fibers increased with time in the compressed segment. Immunohistochemically, the number of cells with expression of nNOS was increased immediately to 12 h after injury. Expression of iNOS was observed from 12 h to 3 days after injury. These findings suggested that the initial maximal increase of NO production might be caused mainly by nNOS and that the second wave of increase in NO might be due mainly to iNOS.

Distractive flexion injuries of the subaxial cervical spine treated with a posterior procedure using cervical pedicle screws or a combined anterior and posterior procedure.

The purpose of this study was to compare the clinical and radiographic outcomes of patients with distractive flexion (DF) injuries of the subaxial cervical spine who had undergone a posterior procedure using cervical pedicle screw (CPS) fixation with those who had undergone a combined anterior and posterior procedure. Recommendations for the surgical treatment of DF injuries of the subaxial cervical spine remain controversial. There are few clinical reports of posterior CPS fixation for DF injuries. We retrospectively reviewed the clinical records and radiographs of 50 consecutive patients with DF injuries of the subaxial cervical spine treated at the Imakiire General Hospital. Group 1 consisted of 24 patients who underwent posterior wiring fixation and fusion with additional anterior decompression and fusion. Group 2 consisted of 26 patients who underwent posterior decompression and fusion with CPS fixation. Group 1 had a significantly longer operation time (295.4 minutes) than Group 2 (163.3 minutes). Group 1 had significantly higher blood loss (689.1g) than Group 2 (313.7 g). No patient in Group 1 or 2 developed postoperative neurological worsening. The mean loss of kyphotic correction was 1.6° and 0.1° in Groups 1 and 2, respectively, and the loss of kyphotic correction in Group 2 was significantly less than that of Group 1. We suggest that posterior procedures with CPS fixation are reasonable for the management of cervical DF injuries.

A newly developed robot suit hybrid assistive limb facilitated walking rehabilitation after spinal surgery for thoracic ossification of the posterior longitudinal ligament: a case report.

Most patients with thoracic ossification of the posterior longitudinal ligament (OPLL) exhibit delayed recovery of gait dysfunction after spinal injury. The hybrid assistive limb (HAL) is a new robot suit controlling knee and hip joint motion by detecting very weak bioelectric signals on the surface of the skin. This study is to report the feasibility and benefits of patient-assistive HAL walking rehabilitation for facilitating locomotor function after spinal surgery. The patient was a 60-year-old woman with thoracic OPLL, and her motor and sensory paralyses did not improve after spinal surgery, indicating severe impairment in the paretic legs. The subject underwent 6 HAL sessions per week for 8 weeks, consisting of a standing and sitting exercise and walking on the ground with HAL. Clinical outcomes were evaluated before and after HAL training and 1 year after surgery. The subject improved considerably as a result of HAL training. Subsequently, her walking ability recovered rapidly, and she was able to walk unaided six months after surgery. This case study suggests that HAL training is a feasible and effective option to facilitating locomotor function and the early HAL training with physiotherapy may enhance motor recovery of patients with residual paralysis after surgery.

Accumulation of p62 in degenerated spinal cord under chronic mechanical compression: functional analysis of p62 and autophagy in hypoxic neuronal cells.

Intracellular accumulation of altered proteins, including p62 and ubiquitinated proteins, is the basis of most neurodegenerative disorders. The relationship among the accumulation of altered proteins, autophagy, and spinal cord dysfunction by cervical spondylotic myelopathy has not been clarified. We examined the expression of p62 and autophagy markers in the chronically compressed spinal cord of tiptoe-walking Yoshimura mice. In addition, we examined the expression and roles of p62 and autophagy in hypoxic neuronal cells. Western blot analysis showed the accumulation of p62, ubiquitinated proteins, and microtubule-associated protein 1 light chain 3 (LC3), an autophagic marker, in the compressed spinal cord. Immunohistochemical examinations showed that p62 accumulated in neurons, axons, astrocytes, and oligodendrocytes. Electron microscopy showed the expression of autophagy markers, including autolysosomes and autophagic vesicles, in the compressed spinal cord. These findings suggest the presence of p62 and autophagy in the degenerated compressed spinal cord. Hypoxic stress increased the expression of p62, ubiquitinated proteins, and LC3-II in neuronal cells. In addition, LC3 turnover assay and GFP-LC3 cleavage assay showed that hypoxic stress increased autophagy flux in neuronal cells. These findings suggest that hypoxic stress induces accumulation of p62 and autophagy in neuronal cells. The forced expression of p62 decreased the number of neuronal cells under hypoxic stress. These findings suggest that p62 accumulation under hypoxic stress promotes neuronal cell death. Treatment with 3-methyladenine, an autophagy inhibitor decreased the number of neuronal cells, whereas lithium chloride, an autophagy inducer increased the number of cells under hypoxic stress. These findings suggest that autophagy promotes neuronal cell survival under hypoxic stress. Our findings suggest that pharmacological inducers of autophagy may be useful for treating cervical spondylotic myelopathy patients.

High mobility group box 1 is upregulated after spinal cord injury and is associated with neuronal cell apoptosis.

STUDY DESIGN: Cerebrocortical culture and rat spinal cord injury (SCI) model were used to examine the expression of high mobility group box 1 (HMGB1), TNF-alpha, and Rage by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemical examination. In addition, relationship between upregulation of HMGB1 and neural cells apoptosis was evaluated after SCI. OBJECTIVE: To evaluate the upregulation of HMGB1, TNF-alpha, and Rage after SCI. SUMMARY OF BACKGROUND DATA: It is known that the mode of delayed neuronal cell death after SCI is apoptosis. Apoptotic cell death is influenced by several injury-promoting factors which include pro-inflammatory cytokines. Inhibition of apoptosis promotes neurologic improvement following SCI. However, the factors which transmit inflammatory signaling following SCI have not yet been clarified in detail. HMGB1 was reported as an important mediator of inflammation. We examined the expression of HMGB1, TNF-alpha and Rage following acute SCI. METHODS: Expression of HMGB1, TNF-alpha and Rage was examined by RT-PCR and immunohistochemical examination. Apoptotic cell death was evaluated by TUNEL methods. RESULTS: HMGB1 was exported from nuclei to cytoplasm in active caspase-3 positive apoptotic cell in vitro. In addition, HMGB1, TNF-alpha, and Rage was expressed in same cell after NMDA treatment. RT-PCR revealed that expression of HMGB1 and TNF-alpha was upregulated following SCI. Immunohistochemical examination revealed that the numbers of HMGB1-, TNF-alpha-, and Rage-positive cells were increased following SCI. The number of TUNEL-positive cells was significantly increased at 12 hours after injury, and was maximal at 72 hours after injury. However, HMGB1- and TNF-alpha-positive cells were maximal in number 48 hours after injury, while Rage-positive cells were maximal in number at 24 hours after injury. These data suggest that HMGB1, TNF-alpha, and Rage were upregulated following SCI but preceding the apoptotic cell death. CONCLUSION: Our findings suggest that HMGB1 play a role in the induction of apoptosis via inflammatory reaction.