Details of a Researcher - Nakamura, Masaya

Papers - Nakamura, Masaya

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Mimicking the neurotrophic factor profile of embryonic spinal cord controls the differentiation potential of spinal progenitors into neuronal cells

Nakamura Masaya, Tsuji Osahiko, Bregman Barbara S., Toyama Yoshiaki, Okano Hideyuki

PLoS ONE 6 ( 6 ) 2011

Recent studies have indicated that the choice of lineage of neural progenitor cells is determined, at least in part, by environmental factors, such as neurotrophic factors. Despite extensive studies using exogenous neurotrophic factors, the effect of endogenous neurotrophic factors on the differentiation of progenitor cells remains obscure. Here we show that embryonic spinal cord derived-progenitor cells express both ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) mRNA before differentiation. BDNF gene expression significantly decreases with their differentiation into the specific lineage, whereas CNTF gene expression significantly increases. The temporal pattern of neurotrophic factor gene expression in progenitor cells is similar to that of the spinal cord during postnatal development. Approximately 50% of spinal progenitor cells differentiated into astrocytes. To determine the effect of endogenous CNTF on their differentiation, we neutralized endogenous CNTF by administration of its polyclonal antibody. Neutralization of endogenous CNTF inhibited the differentiation of progenitor cells into astrocytes, but did not affect the numbers of neurons or oligodendrocytes. Furthermore, to mimic the profile of neurotrophic factors in the spinal cord during embryonic development, we applied BDNF or neurotrophin (NT)-3 exogenously in combination with the anti-CNTF antibody. The exogenous application of BDNF or NT-3 promoted the differentiation of these cells into neurons or oligodendrocytes, respectively. These findings suggest that endogenous CNTF and exogenous BDNF and NT-3 play roles in the differentiation of embryonic spinal cord derived progenitor cells into astrocytes, neurons and oligodendrocytes, respectively. © 2011 Nakamura et al.

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Ball tip technique for thoracic pedicle screw placement in patients with adolescent idiopathic scoliosis

Watanabe Kota, Matsumoto Morio, Takashi Tsuji Ken Ishii, Takaishi Hironari, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro

Journal of Neurosurgery: Spine 13 ( 2 ) 246 - 252 2010.08

ISSN 1547-5654

Object. The aim in this study was to evaluate the efficacy of the ball tip technique in placing thoracic pedicle screws (TPSs), as compared with the conventional freehand technique, in both a cadaveric study and a clinical study of patients with adolescent idiopathic scoliosis. Although posterior spinal surgery using TPSs has been widely applied, these screws are associated with the potential risk of vascular, pulmonary, or neurological complications. To further enhance the accuracy and safety of TPS placement, the authors developed the ball tip technique. Methods. After creating an appropriate starting point for probe insertion, a specially designed ball tip probe consisting of a ball-shaped tip with a flexible metal shaft is used to make a guide hole into the pedicle. Holding the probe with the fingertips while using an appropriate amount of pressure or by tapping it gently and continuously with a hammer, one can safely insert the ball tip probe into the cancellous channel in the pedicle. In a cadaveric study, 5 spine fellows with similar levels of experience in placing TPSs applied the ball tip or the conventional technique to place screws in 5 cadavers with no spinal deformities. The incidence of misplaced screws was evaluated by dissecting the spines. In a clinical study, 40 patients with adolescent idiopathic scoliosis underwent posterior surgery with TPS placement via the ball tip or conventional technique (20 patients in each treatment group). The accuracy of the TPS placements was evaluated on postoperative axial CT scanning. Results. In the cadaveric study, 100 TPSs were evaluated, and the incidence of misplaced screws was 14% in the ball tip group and 34% in the conventional group (p = 0.0192). In the clinical study, 574 TPSs were evaluated. One hundred seventy-one intrapedicular screws (67%) were recognized in the conventional group and 288 (90%) in the ball tip group (p < 0.01). In the conventional and ball tip groups, the respective numbers of TPSs with a pedicle breach of ≤ 2 mm were 20 (8%) and 15 (5%), those with a pedicle breach of > 2 mm were 32 (13%) and 9 (3%; p < 0.01), and those located in the costovertebral joints were 32 (13%) and 7 (2%). Conclusions. In both cadaveric and clinical studies the ball tip technique enhanced the accuracy of TPS placement as compared with the conventional freehand technique. Thus, the ball tip technique is useful for the accurate and safe placement of TPSs in deformed spines.

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Anti-IL-6-receptor antibody promotes repair of spinal cord injury by inducing microglia-dominant inflammation

Mukaino Masahiko, Nakamura Masaya, Yamada Osamu, Okada Seiji, Morikawa Satoru, Renault-Mihara Francois, Iwanami Akio, Ikegami Takeshi, Ohsugi Yoshiyuki, Tsuji Osahiko, Katoh Hiroyuki, Matsuzaki Yumi, Toyama Yoshiaki, Liu Meigen, Okano Hideyuki

Experimental Neurology 224 ( 2 ) 403 - 414 2010.08

ISSN 0014-4886

We previously reported the beneficial effect of administering an anti-mouse IL-6 receptor antibody (MR16-1) immediately after spinal cord injury (SCI). The purpose of our present study was to clarify the mechanism underlying how MR16-1 improves motor function after SCI. Quantitative analyses of inflammatory cells using flow cytometry, and immunohistochemistry with bone marrow-chimeric mice generated by transplanting genetically marked purified hematopoietic stem cells, revealed that MR16-1 dramatically switched the central player in the post-traumatic inflammation, from hematogenous macrophages to resident microglia. This change was accompanied by alterations in the expression of relevant cytokines within the injured spinal cord; the expression of recruiting chemokines including CCL2, CCL5, and CXCL10 was decreased, while that of Granulocyte/Macrophage-Colony Stimulating Factor (GM-CSF), a known mitogen for microglia, was increased. We also showed that the resident microglia expressed higher levels of phagocytic markers than the hematogenous macrophages. Consistent with these findings, we observed significantly decreased tissue damage and reduced levels of myelin debris and Nogo-A, the axonal growth inhibitor, by MR16-1 treatment. Moreover, we observed increased axonal regeneration and/or sprouting in the MR16-1-treated mice. Our findings indicate that the functional improvement elicited by MR16-1 involves microglial functions, and provide new insights into the role of IL-6 signaling in the pathology of SCI. © 2010 Elsevier Inc.

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Risk factors for development of subaxial subluxations following atlantoaxial arthrodesis for atlantoaxial subluxations in rheumatoid arthritis

Ishii Ken, Matsumoto Morio, Takahashi Yuichiro, Okada Eijiro, Watanabe Kota, Tsuji Takashi, Takaishi Hironari, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro

Spine 35 ( 16 ) 1551 - 1555 2010.07

ISSN 0362-2436

Study Design: Retrospective radiographic/imaging study. Objective: To evaluate preoperative and sequential postoperative radiographs following C1-C2 arthrodesis for atlantoaxial subluxation in patients with rheumatoid arthritis (RA) to determine risk factors for the development of subaxial subluxations (SAS). Summary of Background Data: The development of SAS has often been observed after C1-C2 arthrodesis. However, there have been no previous reports on the correlation between radiographic parameters and the incidence of postoperative SAS. Methods: The study group comprised of 58 patients with RA who underwent C1-C2 arthrodesis due to atlantoaxial subluxation. There were 5 men and 53 women with a mean age of 55.8 years. The mean follow-up period was 137 months. Nineteen patients with a postoperative SAS after C1-C2 arthrodesis were classified as the SAS+ group. Other 39 pat ents without a postoperative SAS were included in the SAS- group. Clinical outcomes and plain radiographs were reviewed retrospectively and compared between the 2 groups. Results: The difference between pre- and postoperative atlantoaxial (AA) angles in the SAS+ group was significantly greater than those in the SAS- group (P = 0.039). The C2-C7 angles changed significantly between pre- and postoperative periods in the SAS+ group (P = 0.039), but not in the SAS- group (P = 0.897). It was suggested that a large AA angle and a small C2-C7 angle observed at the early postoperative period were the risk factors for the development of SAS. We also demonstrated that a high incidence of the C3-C4 SAS resulted from excessive bone fusion at the C2-C3. Conclusion: Excessive correction of AA angle is likely to cause loss of cervical lordosis, resulting in the development of postoperative SAS. In addition, extensive bony union at C2-C3 following C1-C2 arthrodesis frequently leads to the development of extensive SAS at the C3-C4. © 2010, Lippincott Williams & Wilkins.

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Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury

Tsuji Osahiko, Miura Kyoko, Okada Yohei, Fujiyoshi Kanehiro, Mukaino Masahiko, Nagoshi Narihito, Kitamura Kazuya, Kumagai Gentaro, Nishino Makoto, Tomisato Shuta, Higashi Hisanobu, Nagai Toshihiro, Katoh Hiroyuki, Kohda Kazuhisa, Matsuzaki Yumi, Yuzaki Michisuke, Ikeda Eiji, Toyama Yoshiaki, Nakamura Masaya, Yamanaka Shinya, Okano Hideyuki

Proceedings of the National Academy of Sciences of the United States of America 107 ( 28 ) 12704 - 12709 2010.07

ISSN 0027-8424

Various types of induced pluripotent stem (iPS) cells have been established by different methods, and each type exhibits different biological properties. Before iPS cell-based clinical applications can be initiated, detailed evaluations of the cells, including their differentiation potentials and tumorigenic activities in different contexts, should be investigated to establish their safety and effectiveness for cell transplantation therapies. Here we show the directed neural differentiation of murine iPS cells and examine their therapeutic potential in amouse spinal cord injury (SCI)model. "Safe" iPS-derived neurospheres, which had been pre-evaluated as nontumorigenic by their transplantation into nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse brain, produced electrophysiologically functional neurons, astrocytes, and oligodendrocytes in vitro. Furthermore, when the safe iPS-derived neurospheres were transplanted into the spinal cord 9 d after contusive injury, they differentiated into all three neural lineages without forming teratomas or other tumors. They also participated in remyelination and induced the axonal regrowth of host 5HT⁺ serotonergic fibers, promoting locomotor function recovery. However, the transplantation of iPSderived neurospheres pre-evaluated as "unsafe" showed robust teratoma formation and sudden locomotor functional loss after functional recovery in the SCI model. These findings suggest that preevaluated safe iPS clone-derived neural stem/progenitor cells may be a promising cell source for transplantation therapy for SCI.

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Transplantation of galectin-1-expressing human neural stem cells into the injured spinal cord of adult common marmosets

Yamane Junichi, Nakamura Masaya, Iwanami Akio, Sakaguchi Masanori, Katoh Hiroyuki, Yamada Masayuki, Momoshima Suketaka, Miyao Sachiyo, Ishii Ken, Tamaoki Norikazu, Nomura Tatsuji, Okano Hirotaka James, Kanemura Yonehiro, Toyama Yoshiaki, Okano Hideyuki

Journal of Neuroscience Research 88 ( 7 ) 1394 - 1405 2010.05

ISSN 0360-4012

Delayed transplantation of neural stem/progenitor cells (NS/PCs) into the injured spinal cord can promote functional recovery in adult rats and monkeys. To enhance the functional recovery after NS/PC transplantation, we focused on galectin-1, a carbohydrate-binding protein with pleiotropic roles in cell growth, differentiation, apoptosis, and neurite outgrowth. Here, to determine the combined therapeutic effect of NS/PC transplantation and galectin-1 on spinal cord injury (SCI), human NS/PCs were transfected by lentivirus with galectin-1 and green fluorescent protein (GFP), (Gal-NS/PCs) or GFP alone (GFP-NS/PCs), expanded in vitro, and then transplanted into the spinal cord of adult common marmosets, 9 days after contusive cervical SCI. The animals' motor function was evaluated by their spontaneous motor activity, bar grip power, and performance on a treadmill test. Histological analyses revealed that the grafted human NS/PCs survived and differentiated into neurons, astrocytes, and oligodendrocytes. There were significant differences in the myelinated area, corticospinal fibers, and serotonergic fibers among the Gal-NS/PC, GFP-NS/PC, vehicle-control, and sham-operated groups. The Gal-NS/PC-grafted animals showed a better performance on all the behavioral tests compared with the other groups. These findings suggest that Gal-NS/PCs have better therapeutic potential than NS/PCs for SCI in nonhuman primates and that human Gal-NS/PC transplantation might be a feasible treatment for human SCI. © 2010 Wiley-Liss, Inc.

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Complicated surgical resection of malignant tumors in the upper cervical spine after failed ion-beam radiation therapy

Matsumoto Morio, Watanabe Kota, Ishii Ken, Tsuji Takashi, Takaishi Hironari, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro, Imanishi Yorihisa, Kishi Kazuo, Kawana Hiromasa

Spine 35 ( 11 ) 2010.05

ISSN 0362-2436

STUDY DESIGN.: Case report. OBJECTIVE.: To report 3 cases of malignant tumors in the upper cervical spine that were treated surgically by a combination of posterior tumor resection and stabilization and anterior tumor resection through a mandible-splitting approach after failed ion-beam radiation therapy. SUMMARY OF BACKGROUND DATA.: Few clinical reports have described in detail the postoperative complications associated with transoral surgical resection of tumors in the upper cervical spine after unsuccessful ion-beam radiation therapy. METHODS.: Three patients with malignant tumors in the upper cervical spine who had undergone ion-beam radiotherapy and experienced tumor recurrence were treated by a combination of posterior and anterior surgery through a mandible-splitting approach. One patient (patient 1, a 32-year-old man) had a hemangioendothelioma at the C2 and C3 level, whereas the other 2 patients (patient 2, a 66-year-old woman and patient 3, a 65-year-old man) had a chordoma at the C2 and C3 level. RESULTS.: The intralesional but macroscopic total resection of the tumors was achieved in all 3 patients. However, serious complications developed after surgery, including deep wound infection, cerebrospinal fluid leakage, and meningitis in patient 1, prolonged swallowing difficulty, subsidence of the strut graft, and recurrence in patient 2, and deep wound infection and discitis causing progressive paralysis in patient 3. All patients underwent salvage surgery, including debridement of the wound in patient 1, posterior reinforcement using instrumentation and posterior tumor resection for the recurrent tumor in patient 2, and anterior debridement of the wound with a pedicle flap using the pectoral major muscle in patient 3 to address these problems. Patients 1 and 3 had no signs of recurrence at the time of a follow-up examination. CONCLUSION.: Severe complications, mainly associated with the disturbance in healing of the retropharyngeal wall, were observed in all 3 patients. A preventive method, such as primary repair of the retropharyngeal wall using muscular/musculocutaneous flaps, should be considered for patients undergoing resection through a transoral approach after ion-beam irradiation. © 2010, Lippincott Williams & Wilkins.

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Posterior decompression surgery for extraforaminal entrapment of the fifth lumbar spinal nerve at the lumbosacral junction

Matsumoto Morio, Watanabe Kota, Ishii Ken, Tsuji Takashi, Takaishi Hironari, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro

Journal of Neurosurgery: Spine 12 ( 1 ) 72 - 81 2010.01

ISSN 1547-5654

Object. In this paper, the authors' goal was to elucidate the clinical features and results of decompression surgery for extraforaminal stenosis at the lumbosacral junction. Methods. Twenty-eight patients with severe leg pain caused by extraforaminal stenosis at the lumbosacral junction (18 men and 10 women; mean age 68.2 ± 8.9 years) were treated by posterior decompression without fusion using a microendoscope in 19 patients and a surgical microscope or loupe in 9 patients. The decompression procedures consisted of partial resection of the sacral ala, the L-5 transverse process, and the L5-S1 facet joint along the L-5 spinal nerve. The following items were investigated: 1) preoperative neurological findings; 2) preoperative radiological findings, including plain radiographs, CT scans, selective radiculography of L-5; 3) surgical outcome as evaluated using the Japanese Orthopaedic Association scale for low-back pain (JOA score); and 4) need for revision surgery. Results. All patients presented with neurological deficits compatible with a diagnosis of L-5 radiculopathy such as weakness of the extensor hallucis longus muscle and sensory disturbance in the L-5 area together with neurogenic claudication. On plain radiographs, 21 patients (75%) and 17 patients (60.7%) exhibited lumbar scoliosis (? 5° ) and wedging of the L5-S1 intervertebral space (≥ 3 ^o ), respectively. The CT scans demonstrated marked osteophyte formation at the posterolateral margin of the L5-S1 vertebral bodies, and a selective L-5 nerve root block was effective in all patients. All patients reported pain relief immediately after surgery. The mean JOA scores were 11.3 ± 3.8 before surgery and 24.3 ± 3.4 at the time of the final follow-up examination; the recovery rate was 68.6 ± 16.5%. The mean estimated blood loss was 66.6 ± 98.6 ml, and the mean surgical time was 135.3 ± 46.5 minutes. No significant difference in the recovery rate of the JOA scores or in the surgical time and blood loss was observed between the 2 surgical approaches. Four patients underwent revision posterior interbody fusion for the recurrence of radicular pain as a result of intraforaminal stenosis in 3 patients and insufficient decompression of the extraforaminal area in the remaining patient at an average of 19.5 months after surgery. Conclusions. Extraforaminal stenosis at the lumbosacral junction is a rare but distinct pathological condition causing L-5 radiculopathy. Decompression surgery without fusion using a microendoscope or a surgical microscope/loupe is a feasible and less invasive surgical option for elderly patients with extraforaminal stenosis at the lumbosacral junction.

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Cordotomy for patients with thoracic malignant astrocytoma

Nakamura Masaya, Tsuji Osahiko, Fujiyoshi Kanehiro, Watanabe Kota, Tsuji Takashi, Ishii Ken, Matsumoto Morio, Toyama Yoshiaki, Chiba Kazuhiro

Journal of Neurosurgery: Spine 13 ( 4 ) 418 - 423 2010

ISSN 1547-5654

Object. The optimal management of malignant astrocytomas remains controversial, and the prognosis of these lesions has been dismal regardless of the administered treatment. In this study the authors investigated the surgical outcomes of cordotomy in patients with thoracic malignant astrocytomas to determine the effectiveness of this procedure. Methods. Cordotomy was performed in 5 patients with glioblastoma multiforme (GBM) and 2 with anaplastic astrocytoma (AA). A Kaplan-Meier survival analysis was performed, and the associations of the resection level with survival and postoperative complications were retrospectively examined. Results. Cordotomy was performed in a single stage in 2 patients with GBM and in 2 stages in 3 patients with GBM and 2 patients with AA. In the 2 patients with GBM, cordotomy was performed 2 and 3 weeks after a partial tumor resection. In the 2 patients with AA, the initial treatment consisted of partial tumor resection and subtotal resection combined with radiotherapy, and rostral tumor growth and progressive paralysis necessitated cordotomy 2 and 28 months later. One patient with a secondary GBM underwent cordotomy; the GBM developed 1 year after subtotal resection and radiotherapy for a WHO Grade II astrocytoma. Four patients died 4, 5, 24, and 42 months after the initial operation due to CSF dissemination, and 3 patients (2 with GBM and 1 with AA) remain alive (16, 39, and 71 months). No metastasis to any other organs was noted. Conclusions. One-stage cordotomy should be indicated for patients with thoracic GBM or AA presenting with complete paraplegia preoperatively. In patients with thoracic GBM, even if paralysis is incomplete, cordotomy should be performed before the tumor disseminates through the CSF. Radical resection should be attempted in patients with AA and incomplete paralysis. If the tumor persists, radiotherapy and chemotherapy are indicated, and cordotomy should be reserved for lesions growing progressively after such second-line treatments.

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Sox10-Venus mice

Shibata Shinsuke, Yasuda Akimasa, Renault-Mihara Francois, Suyama Satoshi, Katoh Hiroyuki, Inoue Takayoshi, Inoue Yukiko U., Nagoshi Narihito, Sato Momoka, Nakamura Masaya, Akazawa Chihiro, Okano Hideyuki

Molecular Brain 3 ( 1 ) 2010

Background. While several mouse strains have recently been developed for tracing neural crest or oligodendrocyte lineages, each strain has inherent limitations. The connection between human SOX10 mutations and neural crest cell pathogenesis led us to focus on the Sox10 gene, which is critical for neural crest development. We generated Sox10-Venus BAC transgenic mice to monitor Sox10 expression in both normal development and in pathological processes. Results. Tissue fluorescence distinguished neural crest progeny cells and oligodendrocytes in the Sox10-Venus mouse embryo. Immunohistochemical analysis confirmed that Venus expression was restricted to cells expressing endogenous Sox10. Time-lapse imaging of various tissues in Sox10-Venus mice demonstrated that Venus expression could be visualized at the single-cell level in vivo due to the intense, focused Venus fluorescence. In the adult Sox10-Venus mouse, several types of mature and immature oligodendrocytes along with Schwann cells were clearly labeled with Venus, both before and after spinal cord injury. Conclusions. In the newly-developed Sox10-Venus transgenic mouse, Venus fluorescence faithfully mirrors endogenous Sox10 expression and allows for in vivo imaging of live cells at the single-cell level. This Sox10-Venus mouse will thus be a useful tool for studying neural crest cells or oligodendrocytes, both in development and in pathological processes. © 2010 Shibata et al; licensee BioMed Central Ltd.

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Microendoscopic resection of lumbar discal cysts

Matsumoto M., Watanabe K., Tsuji T., Ishii K., Takaishi H., Nakamura M., Toyama Y., Chiba K.

Minimally Invasive Neurosurgery 53 ( 2 ) 69 - 73 2010

ISSN 0946-7211

Introduction: A lumbar discal cyst is a relatively rare cystic lesion that communicates with lumbar intervertebral discs. Surgical resection of the cyst is the reported treatment of choice. In this study, the authors report the minimally invasive surgical resection of lumbar discal cysts using a microendoscopy. Patients and Methods: Seven male patients with lumbar discal cysts underwent microendoscopic resections (mean age: 25.1?3.2 years and the mean follow-up period: 27.9 months). During the surgeries, the cysts were subtotally resected in a piecemeal fashion, and the fistulas forming the communications between the cysts and the corresponding intervertebral discs were coagulated using a bipolar coagulator. Results: All the patients obtained relief from their pain after surgery, and no recurrences occurred during a mean follow-up period of 28 months. The mean operation time was 72.6?20.2min, and the mean blood loss was 44.4?13.7 grams. No intra- or peri-operative complications were noted in any of the patients. Conclusions: Microendoscopic resection appears to be a minimally invasive and feasible surgical option for the treatment of lumbar discal cysts. © Georg Thieme Verlag KG Stuttgart.

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Transplantation of dendritic cells promotes functional recovery from spinal cord injury in common marmoset

Yaguchi Masae, Tabuse Masanao, Ohta Shigeki, Ohkusu-Tsukada Kozo, Takeuchi Tamaki, Yamane Junichi, Katoh Hiroyuki, Nakamura Masaya, Matsuzaki Yumi, Yamada Masayuki, Itoh Toshio, Nomura Tatsuji, Toyama Yoshiaki, Okano Hideyuki, Toda Masahiro

Neuroscience Research 65 ( 4 ) 384 - 392 2009.12

ISSN 0168-0102

We previously reported that implantation of dendritic cells (DCs) into the injured site activates neural stem/progenitor cells (NSPCs) and promotes functional recovery after spinal cord injury (SCI) in mice. Working toward clinical application of DC therapy for SCI, we analyzed whether DCs promote functional recovery after SCI in a non-human primate, the common marmoset (CM). CMs are usually born as dizygotic twins. They are thus natural bone marrow and peripheral blood chimeras due to sharing of the placental circulation between dizygotic twins, leading to functional immune tolerance. In this study, to identify adequate CM donor-and-host pairs, mixed leukocyte reaction (MLR) assays were performed. Then, CM-DCs were generated from the bone marrow of the twin selected to be donor and transplanted into the injured site of the spinal cord of the other twin selected to be host, 7 days after injury. Histological analyses revealed fewer areas of demyelination around the injured site in DC-treated CMs than in controls. Immunohistochemical analysis showed that more motor neurons and corticospinal tracts were preserved after SCI in DC-treated CMs. Motor functions were evaluated using three different behavior tests and earlier functional recovery was observed in DC-treated CMs. These results suggest DC therapy to possibly be beneficial in primates with SCI and that this treatment has potential for clinical application. © 2009 Elsevier Ireland Ltd and the Japan Neuroscience Society.

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Quantification of neurotrophins in skeletal muscle following nerve injury

Morisawa Yasushi, Takayama Shinichiro, Nakamura Masaya, Nakamura Toshiyasu, Ikegami Hiroyasu, Toyama Yoshiaki

Journal of Musculoskeletal Research 12 ( 4 ) 205 - 212 2009.12

ISSN 0218-9577

Purpose: We investigated the kinematics of nerve growth factor (NGF)mRNA and brain-derived neurotrophic factor (BDNF)mRNA in a skeletal muscle following spinal cord and peripheral nerve injuries by utilizing the reverse-transcription polymerase chain reaction/high-performance liquid chromatography (RT-PCR/HPLC) method. Methods: We made mice models of spinal cord transection and sciatic nerve transection, plus sham and control groups. After RNA extraction from gastrocnemius muscle of mice, RT-PCR was done. We measured the levels of NGFmRNA and BDNFmRNA in a skeletal muscle following spinal cord and peripheral nerve injuries by utilizing the RT-PCR/HPLC method. All values are analyzed and graphed as means ±SED. Bonferroni test (Post-hoc test) was used when two values were compared. Differences were considered statistically significant when p < 0.05. Results: According to the wet muscle weight, at day 7, a significant difference was found between the peripheral lesion and control group, and at days 14 and 28, significant differences were found between the spinal and peripheral lesion and control group. According to the NGFmRNA, in the peripheral nerve injury group, the levels increased up to day 28 and when compared with the control group, the levels were significantly higher at days 14 and 28. According to the BDNFmRNA, levels at days 2, 7, 14, and 28 were significantly lower in the spinal cord injury group than in the control group. However, in peripheral nerve injury group, when compared with the control group, the levels significantly increased at days 7, 14, and 28. Conclusion: We clarified marked differences in chronological changes in neurotrophin kinetics in a skeletal muscle between spinal cord injury and peripheral nerve injury. © 2009 World Scientific Publishing Company.

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Progressive kyphoscoliosis associated with tethered cord treated by posterior vertebral column resection

Matsumoto Morio, Watanabe Kota, Tsuji Takashi, Ishii Ken, Takaishi Hironari, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro

Spine 34 ( 26 ) 2009.12

ISSN 0362-2436

Study Design: A case report. OBJECTIVES.: To report a case of progressive yphoscoliosis associated with a tethered cord that was corrected by posterior vertebral column resection after complicated untethering surgery. Summary of Background Data: There have been few clinical reports on posterior vertebral column resection conducted for severe deformity associated with a tethered cord. Methods: A patient with progressive kyphoscoliosis associated with a tethered cord first underwent untethering surgery, resulting in neurologic deterioration. Posterior vertebral column resection was performed to correct the kyphoscoliosis while shortening the spinal column to prevent the spinal cord from stretch injury. Results: Good correction of kyphoscoliosis was obtained without further neurologic deterioration. The Cobb angles of scoliosis was 103° before surgery and 25° after surgery (correction rate; 75.7%), and that of kyphosis was 90° and 36°, respectively (correction rate; 60.0%). Conclusion: Correction of progressive kyphoscoliosis associated with a tethered cord can be achieved successfully by posterior vertebral column resection even after complicated untethering surgery. © 2009, Lippincott Williams & Wilkins.

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Roles of ES cell-derived gliogenic neural stem/progenitor cells in functional recovery after spinal cord injury

Kumagai Gentaro, Okada Yohei, Yamane Junichi, Nagoshi Narihito, Kitamura Kazuya, Mukaino Masahiko, Tsuji Osahiko, Fujiyoshi Kanehiro, Katoh Hiroyuki, Okada Seiji, Shibata Shinsuke, Matsuzaki Yumi, Toh Satoshi, Toyama Yoshiaki, Nakamura Masaya, Okano Hideyuki

PLoS ONE 4 ( 11 ) 2009.11

Transplantation of neural stem/progenitor cells (NS/PCs) following the sub-acute phase of spinal cord injury (SCI) has been shown to promote functional recovery in rodent models. However, the types of cells most effective for treating SCI have not been clarified. Taking advantage of our recently established neurosphere-based culture system of ES cell-derived NS/PCs, in which primary neurospheres (PNS) and passaged secondary neurospheres (SNS) exhibit neurogenic and gliogenic potentials, respectively, here we examined the distinct effects of transplanting neurogenic and gliogenic NS/PCs on the functional recovery of a mouse model of SCI. ES cell-derived PNS and SNS transplanted 9 days after contusive injury at the Th10 level exhibited neurogenic and gliogenic differentiation tendencies, respectively, similar to those seen in vitro. Interestingly, transplantation of the gliogenic SNS, but not the neurogenic PNS, promoted axonal growth, remyelination, and angiogenesis, and resulted in significant locomotor functional recovery after SCI. These findings suggest that gliogenic NS/PCs are effective for promoting the recovery from SCI, and provide essential insight into the mechanisms through which cellular transplantation leads to functional improvement after SCI. © 2009 Kumagai et al.

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Long-Term surgical outcomes for myxopapillary ependymomas of the Cauda equina

Nakamura Masaya, Ishii Ken, Watanabe Kota, Tsuji Takashi, Matsumoto Morio, Toyama Yoshiaki, Chiba Kazuhiro

Spine 34 ( 21 ) 2009.10

ISSN 0362-2436

Study Design. Retrospective case series. Objective. To evaluate our treatment strategy for myxopapillary ependymomas of the cauda equina. Summary of Background Data. Some patients with myxopapillary ependymoma develop cerebrospinal fluid (CSF) dissemination leading to poor prognosis. Because of the rarity of this tumor, there is no consensus on its optimal treatment options and prognosis. Methods We reviewed 25 cases of myxopapillary ependymomas, treated surgically between 1972 and 2005. The mean postoperative follow-up period was 10.4 years. The effects of surgical margins at surgery and postoperative radiotherapy on tumor recurrence and prognosis were investigated. Results In 15 patients, total resection achieved (6 cases of en bloc resection without postoperative radiation, and in 9 cases piecemeal resection) was followed by whole brain and spinal cord radiation or local irradiation. Fourteen of these patients survived without tumor recurrence. In 1 case of total resection without radiotherapy, the tumor capsule was violated intraoperatively and local recurrence occurred 2 years after surgery. In 4 patients, the tumors were removed subtotally. Of these, 2 patients who received radiation (24 Gy) only to the whole brain and spinal cord developed recurrence, and 2 who received whole brain and spinal cord radiation (24 Gy) supplemented with local radiation (46 Gy) developed no recurrence. The remaining 6 patients received partial resection after local radiation (40-50 Gy) alone, and all 6 died of CSF dissemination. Conclusion. The results of the present study indicate that the surgical margin obtained at the initial surgery and the extent and amount of postoperative radiation can be crucial factors determining the prognosis of patients with myxopapillary ependymoma. Although this tumor is histologically benign, CSF dissemination can occur once tumor capsule is violated, before or during surgery. Therefore, early diagnosis is essential, and a therapeutic strategy including radiotherapy, on the assumption that this tumor is malignant, should be established. © 2009, Lippincott Williams & Wilkins.

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Neural crest-derived stem cells display a wide variety of characteristics

Nagoshi Narihito, Shibata Shinsuke, Nakamura Masaya, Matsuzaki Yumi, Toyama Yoshiaki, Okano Hideyuki

Journal of Cellular Biochemistry 107 ( 6 ) 1046 - 1052 2009.08

ISSN 0730-2312

A recent burst of findings has shown that neural crest-derived stem cells (NCSCs) can be found in diverse mammalian tissues. In addition to their identification in tissues that are known to be derived from the neural crest, recent studies have revealed NCSCs in tissues that are not specifically derived from the neural crest, such as bone marrow. NCSCs can express a wide range of characteristics, and which properties are expressed mainly depends on their tissue sources and the ontogenic stage of the animal. The identification of NCSCs in various tissues opens an entirely new avenue of approach to developing autologous cell replacement therapies for use in regenerative medicine. In this review, we discuss the origin, migration, and lineage potential of NCSCs from various mammalian tissue sources. © 2009 Wiley-Liss, Inc.

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Intramedullary solitary fibrous tumor of the spinal cord

Ishii Ken, Nakamura Masaya, Matsumoto Morio, Mukai Makio, Toyama Yoshiaki, Chiba Kazuhiro

Journal of Orthopaedic Science 14 ( 4 ) 450 - 454 2009.07

ISSN 0949-2658

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Clinical significance and prognosis of idiopathic syringomyelia

Nakamura Masaya, Ishii Ken, Watanabe Kota, Tsuji Takashi, Matsumoto Morio, Toyama Yoshiaki, Chiba Kazuhiro

Journal of Spinal Disorders and Techniques 22 ( 5 ) 372 - 375 2009.07

ISSN 1536-0652

STUDY DESIGN: Retrospective case series. OBJECTIVE: To determine the clinical significance and prognosis of idiopathic syringomyelia. SUMMARY OF BACKGROUND DATA: With the widespread use of magnetic resonance imaging, cases of syringomyelia are found occasionally. However, the clinical significance and optimum treatment strategy for idiopathic syringomyelia remain unclear, because there are few reports on details of this condition. METHODS: The clinical records and magnetic resonance images of 15 patients with idiopathic syringomyelia were reviewed to determine the changes in patient's neurologic status assessed by the Japanese Orthopedic Association scores for cervical myelopathy and the distribution of the syringomyelia on magnetic resonance imaging. Twelve cases were treated conservatively (conservative group) and syringo-subarachnoid shunt was performed in the remaining 3 cases (surgical group). The follow-up period ranged from 7 to 20 years (mean: 10.5 y). RESULTS: The localized type of idiopathic syringomyelia, which extended under 3 vertebras (mean: 2.1 vertebras), was observed in the 12 patients of the conservative group. There were no significant changes in either the size of the syringomyelia or the severity of the neurologic deficits during the follow-up period (mean: 10 y). In contrast, the extended type, which distributed over 4 or more vertebras (mean: 10.2 vertebras), was observed in the 3 patients of the surgical group. Because of severe and progressive neurologic deficits, syringo-subarachnoid shunt was performed and the surgery successfully prevented further neurologic deterioration. The mean Japanese Orthopedic Association score of the surgical group was significantly lower than that of the conservative group, both at the time of the initial examination and at the final follow-up. CONCLUSIONS: There are 2 types of idiopathic syringomyelia. One is a "localized" type, which might represents congenital enlargement of the central canal of the spinal cord, and can be managed conservatively. The other is an "extended" type, which causes progressive neurologic dysfunction, and should be treated surgically to prevent further neurologic deterioration. Further study should be needed to clarify the mechanism of the extended type of idiopathic syringomyelia. © 2009 Lippincott Williams & Wilkins, Inc.

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Nocturnal leg cramps

Matsumoto Morio, Watanabe Kota, Tsuji Takashi, Ishii Ken, Takaishi Hironari, Nakamura Masaya, Toyama Yoshiaki, Chiba Kazuhiro, Michikawa Takehiro, Nishiwaki Yuji

Spine 34 ( 5 ) 2009.03

ISSN 0362-2436

STUDY DESIGN.: Questionnaire survey on leg cramps for patients with lumbar spinal canal stenosis (LCS). OBJECTIVE.: To evaluate the prevalence of leg cramps in patients with LCS treated surgically and the relationship between leg cramps and the surgical outcomes. SUMMARY OF BACKGROUND DATA.: Although it has been anecdotally reported that LCS patients have suffered from leg cramps, the true prevalence remains unknown. METHODS.: One hundred twenty LCS patients who underwent decompression surgery (men 85, women 35, mean age 73.5) and 370 elderly subjects from the general population (men 162, women 208, mean age 75.6) were enrolled in the study. The participants filled in a questionnaire regarding: (all participants) (1) experience of leg cramps, (2) frequency and time of the day of the cramp attacks; (for LCS patients only), (3) changes in cramps before and after surgery, (4) activities of daily living disturbance because of leg cramps, (5) satisfaction with surgery and walking ability, (6) the Roland-Morris Disability Questionnaire, and (7) the Oswestry Disability Index. RESULTS.: Eighty-five (70.8%) patients with LCS and 137 (37.2%) of the control population experienced leg cramps (age and sex adjusted odds ratio; 4.6, P < 0.01). Leg cramps occurred once or twice a week in 34.9% of the LCS group and once in several months in 44.5% of the control group, and occurred nocturnally in 73.3% of the LCS patients and in 91.6% of the control group. In LCS patients, leg cramps improved after surgery in 18.2%, remained unchanged in 45.5%, and worsened in 26.1%, and activities of daily living were disturbed in 47.6%. There was no significant difference in satisfaction with surgery, the Oswestry Disability Index, the Roland-Morris Disability Questionnaire scores, or walking ability between the LCS patients with or without leg cramps. CONCLUSION.: LCS patients had significantly more frequent attacks of nocturnal leg cramps than the control population, and leg cramps disturbed the quality of the patients' life, and they rarely improved after decompression surgery. Leg cramps should be recognized as one of the symptoms of LCS, which disturb the patients' quality of life. © 2009, Lippincott Williams & Wilkins.

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