Spinal cord injury (SCI) often leads to persistent functional deficits due to loss of neurons and glia and to limited axonal regeneration after injury. Here we report that transplantation of human dental pulp stem cells into the completely transected adult rat spinal cord resulted in marked recovery of hind limb locomotor functions. Transplantation of human bone marrow stromal cells or skin-derived fibroblasts led to substantially less recovery of locomotor function. The human dental pulp stem cells exhibited three major neuroregenerative activities. First, they inhibited the SCI-induced apoptosis of neurons, astrocytes, and oligodendrocytes, which improved the preservation of neuronal filaments and myelin sheaths. Second, they promoted the regeneration of transected axons by directly inhibiting multiple axon growth inhibitors, including chondroitin sulfate proteoglycan and myelin-associated glycoprotein, via paracrine mechanisms. Last, they replaced lost cells by differentiating into mature oligodendrocytes under the extreme conditions of SCI. Our data demonstrate that tooth-derived stem cells may provide therapeutic benefits for treating SCI through both cell-autonomous and paracrine neuroregenerative activities.
We have reviewed 1858 patients who had undergone a cervical laminoplasty and identified 43 (2.3%) who had developed a C5 palsy with a MMT (MRC) grade of 0 to 2 in the deltoid, with or without involvement of the biceps, but with no loss of muscular strength in any other muscles. The clinical features and radiological findings of patients with (group P; 43 patients) and without (group C; 100 patients) C5 palsy were compared. CT scanning of group P revealed a significant narrowing of the intervertebral foramen of C5 (p < 0.005) and a larger superior articular process (p < 0.05). On MRI, the posterior shift of the spinal cord at C4-5 was significantly greater in group P, than in group C (p < 0.01). This study is the first to correlate impairment of the C5 nerve root with a C5 palsy. It may be that early foraminotomy in susceptible individuals and the avoidance of tethering of the cord by excessive laminoplasty may prevent a post-operative palsy of the C5 nerve root.
Engrafted mesenchymal stem cells from human deciduous dental pulp (SHEDs) support recovery from neural insults via paracrine mechanisms that are poorly understood. Here we show that the conditioned serum-free medium (CM) from SHEDs, administered intrathecally into rat injured spinal cord during the acute postinjury period, caused remarkable functional recovery. The ability of SHED-CM to induce recovery was associated with an immunoregulatory activity that induced anti-inflammatory M2-like macrophages. Secretome analysis of the SHED-CM revealed a previously unrecognized set of inducers for anti-inflammatory M2-like macrophages: monocyte chemoattractant protein-1 (MCP-1) and the secreted ectodomain of sialic acid-binding Ig-like lectin-9 (ED-Siglec-9). Depleting MCP-1 and ED-Siglec-9 from the SHED-CM prominently reduced its ability to induce M2-like macrophages and to promote functional recovery after spinal cord injury (SCI). The combination of MCP-1 and ED-Siglec-9 synergistically promoted the M2-like differentiation of bone marrow-derived macrophages in vitro, and this effect was abolished by a selective antagonist for CC chemokine receptor 2 (CCR2) or by the genetic knock-out of CCR2. Furthermore, MCP-1 and ED-Siglec-9 administration into the injured spinal cord induced M2-like macrophages and led to a marked recovery of hindlimb locomotor function after SCI. The inhibition of this M2 induction through the inactivation of CCR2 function abolished the therapeutic effects of both SHED-CM and MCP-1/ED-Siglec-9. Macrophages activated by MCP-1 and ED-Siglec-9 extended neurite and suppressed apoptosis of primary cerebellar granule neurons against the neurotoxic effects of chondroitin sulfate proteoglycans. Our data suggest that the unique combination of MCP-1 and ED-Siglec-9 repairs the SCI through anti-inflammatory M2-like macrophage induction.
With aging of society, clarification of the relationship between QOL and abnormal posture in the elderly may allow improvement of QOL through any preventive methods and training. However, sagittal balance has not been studied widely and most studies have focused on postmenopausal patients with osteoporosis. In this report, we provide the first evaluation of the simultaneous effects of degenerative changes on radiograph, spinal range of motion (ROM), sagittal balance, and back muscle strength, and examine the influence of these effects on QOL of the middleaged and elderly male subjects. The subjects were 100 Japanese males who underwent a basic health checkup. Lumbar lateral radiograph, sagittal balance and spinal mobility determined with SpinalMouse Ò and back muscle strength were measured. The thoracic/lumbar angle ratio (T/L ratio) was used as an index of sagittal balance. SF-36 physical component summary (PCS) scores showed a significant negative correlation with age (r = -0.377), osteophyte score (r = -0.246) and T/L ratio (r = -0.214), and a significant positive correlation with lumbar lordosis angle (r = 0.271), thoracic ROM (r = 0.282), and back muscle strength (r = 0.549). Multiple regression analysis indicated that thoracic spinal ROM (r = 0.254, p \ 0.01) and back muscle strength (r = 0.488, p \ 0.0001) were significantly associated with SF-36 PCS (R 2 = 0.403).In conclusion, QOL of the middle-aged and elderly male subjects was related to sagittal balance, lumbar lordosis angle, spinal ROM, and back muscle strength. Exercise including muscle strength and spinal ROM may be able to influence these primary factors related to QOL. Back muscle strength and thoracic ROM impact on improvement of QOL in the middle-aged and the elderly.
Purpose To clarify the relative frequency of various histopathological primary spinal cord tumors and their features in Japanese people and to compare this data with other reports. Methods Primary spinal cord tumor surgical cases from 2000 to 2009, which were registered in our affiliated hospital database were collected. We examined age at surgery, sex, anatomical location, vertebral level of the tumor, and pathological diagnosis in each case.Results Of the 678 patients in our study, 377 patients (55.6 %) were males and 301 patients (44.4 %) were females (male/female ratio 1.25). The mean age at surgery was 52.4 years. Of these tumors, 123 cases (18.1 %) were intramedullary, 371 cases (54.7 %) were intradural extramedullary, 28 cases (4.1 %) were epidural, and 155 cases (22.9 %) were dumbbell tumors. The pathological diagnoses included 388 schwannomas (57.2 %), 79 meningiomas (11.6 %), 54 ependymomas (8.0 %), 27 hemangiomas (4.0 %), 23 hemangioblastomas (3.4 %), 23 neurofibromas (3.4 %), and 9 astrocytomas (1.3 %). The male/female ratios for schwannomas, meningiomas, ependymomas,Department of Orthopaedic Surgery, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8560, Japan e-mail: imagama@med.nagoya-u.ac.jp K. Sato Department of Orthopaedic Surgery, Nagoya Daini Red Cross Hospital, 2-9, Myoken-cho, Showa-ku, Nagoya 466-8650, Japan (2012( ) 21:2019( -2026( DOI 10.1007( /s00586-012-2345 hemangiomas, hemangioblastomas, neurofibromas, malignant lymphomas, and lipomas are 1.4, 0.34, 1.3, 1.5, 2.3, 1.3, 2.7 and 2.3, respectively. Conclusion This is the first published research in English on the epidemiology of primary spinal cord tumors in Japanese people. Similar to other reports from Asian countries, our data indicates a higher male/female ratio overall for spinal cord tumors, a higher proportion of nerve sheath cell tumors, and a lower proportion of meningiomas and neuroepithelial tumors compared to reports from non-Asian countries. Data in the current study represent the characteristics of primary spinal cord tumors in Asian countries.
Objective Risk factors for falling in elderly people remain uncertain, and the effects of spinal factors and physical ability on body balance and falling have not been examined. The objective of this study was to investigate how factors such as spinal sagittal alignment, spinal range of motion, body balance, muscle strength, and gait speed influence falling in the prospective cohort study. Methods The subjects were 100 males who underwent a basic health checkup. Balance, SpinalMouse Ò data, grip strength, back muscle strength, 10-m gait time, lumbar lateral standing radiographs, body mass index, and fall history over the previous year were examined. Platform measurements of balance included the distance of movement of the center of pressure (COP) per second (LNG/TIME), the envelopment area traced by movement of the COP (E AREA), and the LNG/E AREA ratio. The thoracic/lumbar angle ratio (T/L ratio) and sagittal vertical axis (SVA) were used as an index of sagittal balance. Results LNG/TIME and E AREA showed significant positive correlations with age, T/L ratio, SVA, and 10-m gait time; and significant negative correlations with lumbar lordosis angle, sacral inclination angle, grip strength and back muscle strength. Multiple regression analysis showed significant differences for LNG/TIME and E AREA with T/L ratio, SVA, lumbar lordosis angle and sacral inclination angle (R 2 = 0.399). Twelve subjects (12 %) had experienced a fall over the past year. Age, T/L ratio, SVA, lumbar lordosis angle, sacral inclination angle, grip strength, back muscle strength, 10-m gait time, height of the intervertebral disc, osteophyte formation in radiographs and LNG/E AREA differed significantly between fallers and non-fallers. The group with SVA [ 40 mm (n = 18) had a significant higher number of subjects with a single fall (6 single fallers/18: p = 0.0075) and with multiple falls (4 multiple fallers/18: p = 0.0095). Conclusion Good spinal sagittal alignment, muscle strength and 10-m gait speed improve body balance and reduce the risk of fall. Muscle strength and physical ability are also important for spinal sagittal alignment. Body balance training, improvement of physical abilities including muscle training, and maintenance of spinal sagittal alignment can lead to prevention of fall.
Study Design. Prospective multicenter study. Objective. To analyze the incidence of intraoperative spinal neuromonitoring (IONM) alerts and neurological complications, as well as to determine which interventions are most effective at preventing postoperative neurological complications following IONM alerts in high risk spinal surgeries. Summary of Background Data. IONM may play a role in identifying and preventing neural damage; however, few studies have clarified the outcomes of intervention after IONM alerts. Methods. We analyzed 2867 patients who underwent surgery for high risk spinal pathology using transcranial electrical motor-evoked potentials from 2010 to 2016. The high-risk spinal surgery cases consisted of 1009 spinal deformity cases, 622 cervical ossification of posterior longitudinal ligament (OPLL) cases, 249 thoracic-OPLL cases, 771 extramedullary spinal cord tumor cases, and 216 intramedullary spinal cord tumor (IMSCT) cases. We set a 70% amplitude reduction as the alarm threshold for transcranial electrical motor-evoked potentials and analyzed the outcomes of the interventions following monitoring alerts and postoperative neurological deficits. Results. The true positive, false positive, true negative, false negative, and rescue cases of IONM comprised 126, 234, 2362, 9, and 136 cases, respectively. Most alerts and interventions occurred during correction and release in deformity cases, posterior decompression and dekyphosis in OPLL cases, and tumor resection and surgery suspension with steroid injection in spinal cord tumor cases; however, individual interventions varied. The rescue rates (number of patients rescued with intervention after IONM alert/number of true positive cases plus rescue cases) for deformity, cervical-OPLL, thoracic--OPLL, extramedullary spinal cord tumor, and IMSCT cases were 61.4% (35/57), 82.1% (32/39), 40% (20/50), 52.5% (31/59), and 31.6% (18/57), respectively. Conclusion. Our prospective multicenter study identified potential neural damage in 9.5% of cases and 52% rescue cases using IONM. Although the rescue ratios for t-OPLL and IMSCT were relatively low, appropriate intervention immediately after an IONM alert may prevent neural damage even in high-risk spinal surgeries. Level of Evidence: 3
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