Contribution of bone marrow‐derived endothelial progenitor cells to neovascularization and astrogliosis following spinal cord injury

Kamei, Naosuke,Kwon, Sang‐,Mo,Kawamoto, Atsuhiko,Ii, Masaaki,Ishikawa, Masakazu,Ochi, Mitsuo,Asahara, Takayuki Wiley Subscription Services, Inc., A Wiley Company 2012 Journal of neuroscience research Vol.90 No.12

<P><B>Abstract</B></P><P>Spinal cord injury causes initial mechanical damage, followed by ischemia‐induced, secondary degeneration, worsening the tissue damage. Although endothelial progenitor cells (EPCs) have been reported to play an important role for pathophysiological neovascularization in various ischemic tissues, the EPC kinetics following spinal cord injury have never been elucidated. In this study, we therefore assessed the in vivo kinetics of bone marrow‐derived EPCs by EPC colony‐forming assay and bone marrow transplantation from Tie2/lacZ transgenic mice into wild‐type mice with spinal cord injury. The number of circulating mononuclear cells and EPC colonies formed by the mononuclear cells peaked at day 3 postspinal cord injury. Bone marrow transplantation study revealed that bone marrow‐derived EPCs recruited into the injured spinal cord markedly increased at day 7, when neovascularization and astrogliosis drastically occurred in parallel with axon growth in the damaged tissue. To elucidate further the contribution of EPCs to recovery after spinal cord injury, exogenous EPCs were systemically infused immediately after the injury. The administered EPCs were incorporated into the injured spinal cord and accelerated neovascularization and astrogliosis. These findings suggest that bone marrow‐derived EPCs may contribute to the tissue repair by augmenting neovascularization and astrogliosis following spinal cord injury. © 2012 Wiley Periodicals, Inc.</P>

Endothelial progenitor cells promote astrogliosis following spinal cord injury through Jagged1-dependent Notch signaling.

Kamei, Naosuke,Kwon, Sang-Mo,Ishikawa, Masakazu,Ii, Masaaki,Nakanishi, Kazuyoshi,Yamada, Kiyotaka,Hozumi, Katsuto,Kawamoto, Atsuhiko,Ochi, Mitsuo,Asahara, Takayuki M.A. Liebert 2012 JOURNAL OF NEUROTRAUMA - Vol.29 No.9

<P>Interactions between endothelial and neural stem cells are believed to play a critical role in the kinetics of neural stem cells in the central nervous system. Here we demonstrate that endothelial progenitor cells promote the repair of injured spinal cord through the induction of Notch-dependent astrogliosis and vascular regulation. The transplantation of Jagged1(+/+) endothelial progenitor cells, but not Jagged1(-/-) endothelial progenitor cells, increased the number of reactive astrocytes during the acute phase, and improved functional recovery following spinal cord injury. Expression of the Notch effector Hes5 was upregulated in the injured spinal cord after Jagged1(+/+) endothelial progenitor cell transplantation. Furthermore, we found that the Notch ligand Delta-like-1 was highly expressed in Jagged1(-/-) endothelial progenitor cells. Transplantation of Delta-like-1, as well as Jagged1-overexpressing 3T3 cells, revealed that only Jagged1-overexpressing 3T3 stromal cells enhanced astrogliosis following spinal cord injury. In addition, Jagged1(+/+) endothelial progenitor cells exhibited not only dramatic pro-angiogenic effects, but also morphologically abnormal vessel stabilization, compared with Jagged1(-/-)endothelial progenitor cells in injured spinal cord. Thus, transplanted endothelial progenitor cells promote astrogliosis, vascular regulation, and spinal cord regeneration through activation of Jagged1-Notch signaling.</P>

Quantitative Assessment of Bone Marrow Edema in Adolescent Athletes with Lumbar Spondylolysis Using Contrast Ratio on Magnetic Resonance Imaging

Nakamae Toshio,Kamei Naosuke,Tamura Takayuki,Kanda Tsukasa,Nakanishi Kazuyoshi,Adachi Nobuo 대한척추외과학회 2021 Asian Spine Journal Vol.15 No.5

Study Design: Prospective cohort study. Purpose: To quantitatively evaluate bone marrow edema (BME) in the pedicle on magnetic resonance imaging (MRI) for adolescent athlete patients with spondylolysis. Overview of Literature: Spondylolysis, a stress fracture of the pars interarticularis, is a common occurrence in adolescent athletes with low back pain. T2-weighed fat-saturated MRI is reportedly useful for the detection of BME in the pedicle in the early stage of spondylolysis; however, to our knowledge, the quantitative assessment of BME in spondylolysis has not been reported. Methods: Adolescent athletes with spondylolysis, including those with symptoms of low back pain, were enrolled. The sporting activity of the patients was restricted, and a hard brace was attached to the spine. The BME range of interest was taken on T2-weighed fat-saturated MRI, and the signal intensity (SI) of the BME (SIedema) was measured. The contrast ratio (CR) between the SI of the BME and SI of the spinal cord (SIcord) was calculated per the following formulae: CRedema=(SIedema–SIcord)/(SIedema+SIcord). The CR of the normal pedicle was measured as a control per the following formulae: CRcontrol=(SIcontrol–SIcord)/(SIcontrol+SIcord). Results: The study enrolled 32 men and one woman; the mean patient age was 15.2 years (range, 12–18 years). The average CR of the edema and normal pedicle at the first visit was 0.506 (range, 0.097–0.804) and 0.137 (range, -0.741 to 0.572), respectively. The CR of the edema was significantly higher as compared to that of the normal pedicle (p<0.01). MRI that was performed 1 month after the first visit showed that the CR of the edema had decreased to 0.204 (range, -0.152 to 0.517). The CR of the edema 1 month thereafter was significantly lower than that at the first visit (p<0.01). Conclusions: Quantitative assessment of BME using CR on MRI is useful in the evaluation of the healing process of spondylolysis.

Quantifying Bone Marrow Edema Adjacent to the Lumbar Vertebral Endplate on Magnetic Resonance Imaging: A Cross-Sectional Study of Patients with Degenerative Lumbar Disease

Nakamae Toshio,Kamei Naosuke,Fujimoto Yoshinori,Yamada Kiyotaka,Tamura Takayuki,Tsuchikawa Yuji,Morisako Taiki,Harada Takahiro,Maruyama Toshiaki,Adachi Nobuo 대한척추외과학회 2022 Asian Spine Journal Vol.16 No.2

Study Design: Cross-sectional study. Purpose: We aimed to quantitatively assess bone marrow edema (BME) on magnetic resonance imaging (MRI) for patients with degenerative lumbar diseases. Overview of Literature: BME adjacent to a sclerotic endplate of the lumbar spine, detected using T2-weighted fat-saturated MRI, is closely associated with low back pain in patients with degenerative lumbar diseases. However, currently, there no quantitative evaluation methods for BME adjacent to the vertebral endplate. Methods: Patients with degenerative lumbar diseases, whose MRIs detected BME, were enrolled. On a T2-weighted fat-saturated MRI, BME appeared as a high-intensity region adjacent to the vertebral endplate. We calculated the contrast ratios (CRs) of BME and normal bone marrow using the signal intensities of BME, normal bone marrow, and the spinal cord. On computed tomography, we calculated Hounsfield unit (HU) values in the same area as BME, the sclerotic endplate, and normal bone marrow to assess bone density. Results: There were 16 men and 14 women, with an average age of 73.5 years. The mean CRs of BME and normal bone marrow were −0.015±0.056 and −0.407±0.023, respectively. BME’s CR was significantly higher than that of normal bone marrow (p<0.01). The HU values in the same area as BME, the sclerotic endplate, and normal bone marrow were 251.9±24.6, 828.3±35.6, and 98.1±9.3, respectively; these values were significantly different from each other (p<0.01). Conclusions: The CR on MRI is a useful quantitative assessment tool for BME in patients with degenerative lumbar diseases.

Immediate Closed Reduction Technique for Cervical Spine Dislocations

Oae Kazunori,Kamei Naosuke,Sawano Makoto,Yahata Tadashi,Morii Hokuto,Adachi Nobuo,Inokuchi Koichi 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.5

Study Design: Retrospective study.Purpose: This research aimed to assess the clinical outcomes of patients with traumatic cervical spine dislocation who underwent closed reduction employing our approach.Overview of Literature: Bedside closed reduction is the quickest procedure for repairing traumatic cervical spine dislocations; nevertheless, it also possesses the risk of neurological deterioration.Methods: For closed reduction, the patient’s head was elevated on a motorized bed, the cervical spine was placed at the midline, traction of 10 kg was applied, the motorized bed was gradually returned to a flat position, the head was lifted off the bed, and the cervical spine was slowly adjusted to a flexed position. The weight of traction was elevated by 5-kg increments until the positional shift was attained. Subsequently, the bed was gradually tilted while traction was applied again to return the cervical spine to the midline position.Results: Of the 43 cases of cervical spine dislocation, closed reduction was carried out in 40 cases, of which 36 were successful. During repositioning, three patients experienced a temporary worsening of their neck pain and neurological symptoms that enhanced when the cervical spine was flexed. Closed reduction was conducted while the patient was awake; nevertheless, sedation was needed in three cases. Among the 24 patients whose pretreatment paralysis had been characterized by American Spinal Injury Association Impairment Scale (AIS) grades A–C, seven patients (29.2%) demonstrated an enhancement of two or more AIS grades at the last observation.Conclusions: Our closed reduction approach safely repaired traumatic cervical spine dislocations.

Physical Signs and Clinical Features of Cervical Myelopathy in Elderly Patients, Especially 80 Years or Older: Comparison of 100 Consecutive Operative Cases across Three Age Groups

Hamasaki Takahiko,Nakamae Toshio,Kamei Naosuke,Fujiwara Yasushi,Rhee John M.,Tanaka Nobuhiro,Fujimoto Yoshinori,Adachi Nobuo,Shimose Shoji 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.5

Study Design: Retrospective cohort study.Purpose: The present study aimed to examine the characteristics of physical signs in elderly patients with cervical myelopathy (CM) and to compare the findings in three different age groups.Overview of Literature: As the global population ages, the incidence of CM in elderly patients is increasing.Methods: We evaluated 100 consecutive surgical patients with CM and divided them into the following groups: 80s (34 patients; mean age, 83.9 years), 70s (33 patients; mean age, 73.9 years), and 69 or younger (33 patients; mean age, 60.9 years). The clinical symptoms and physical signs were evaluated and recorded.Results: Although the recovery rate decreased with increasing age, all groups demonstrated a significant improvement in clinical symptoms relative to preoperative values. The Hoffman sign and hyperreflexia of the triceps tendon were, respectively, present in 82% and 88% of patients in the 80s group, 74% and 64% of those in the 70s group, and 69% and 82% of those in the 69 or younger group, with no significant difference among the groups. In contrast, the rates of hyperreflexia of the patellar and Achilles tendons were, respectively, 59% and 32% in the 80s group, 85% and 48% in the 70s group, and 91% and 70% in the 69 or younger group, with significant differences.Conclusions: The positivity rate of the lower extremity hyperreflexia decreased significantly with increasing age in patients with CM. The absence of hyperreflexia, particularly lower extremity, is not uncommon in elderly patients with suspected CM.

Novel Hybrid Hydroxyapatite Spacers Ensure Sufficient Bone Bonding in Cervical Laminoplasty

Nobuhiro Tanaka,Kazuyoshi Nakanishi,Naosuke Kamei,Toshio Nakamae,Shinji Kotaka,Yoshinori Fujimoto,Mitsuo Ochi,Nobuo Adachi 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.6

Study Design: Prospective observational study. Purpose: This prospective analysis aimed to evaluate the efficacy and bone-bonding rate of hybrid hydroxyapatite (HA) spacers in expansive laminoplasty. Overview of Literature: Various types of spacers or plates have been developed for expansive laminoplasty. Methods: Expansive open-door laminoplasty was performed in 146 patients with cervical myelopathy; 450 hybrid HA spacers and 41 autogenous bone spacers harvested from the spinous processes were grafted into the opened side of each lamina. The patients were followed up using computed tomography (CT), and their bone-bonding rates for hybrid HA and autogenous spacers, bone-fusion rates of the hinges of the laminae, and complications associated with the implants were then examined. Results: Clinical symptoms significantly improved in all patients, and no major complications related to the procedure were noted. The hybrid HA spacers exhibited sufficient bone bonding on postoperative CT. The hinges completely fused in over 95% patients within 1 year of the procedure. Only 4 spacers (0.9%) developed lamina sinking, and most expanded laminae maintained their positions without sinking or floating throughout the follow-up period. Conclusions: Hybrid HA spacers contributed to high bone-fusion rates of the spacers and hinges of the laminae, and no complications were associated with their use. Cervical laminoplasty with these spacers is safe and simple, and it yields sufficient fixation strength while ensuring sufficient bone bonding during the immediate postoperative period.

Foramen Magnum Decompression with Outer Dura Matter Layer Resection for Chiari Type I Malformation: Factors Correlated with Syrinx Reduction

Maruyama Toshiaki,Nakamae Toshio,Kamei Naosuke,Tanaka Nobuhiro,Fujiwara Yasushi,Harada Takahiro,Adachi Nobuo 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.2

Study Design: A retrospective cohort study.Purpose: We aimed to investigate the surgical results of foramen magnum decompression (FMD) to identify the potential factors associated with syrinx reduction in Chiari malformation type I (CMI).Overview of Literature: The predictive value of preoperative factors for syrinx reduction in patients with CMI remains debatable.Methods: We enrolled patients who underwent microscopic FMD with outer dural layer resection for CMI. The distance from the tip of the cerebellar tonsil to the C2 vertebral endplate on sagittal magnetic resonance imaging (MRI) was defined as the tonsillar distance (TD). Patients who showed a >20% syrinx diameter reduction on the 1-year follow-up MRI were defined as the syrinx reduction group while the others were categorized in the syrinx nonreduction group. Patients with syringomyelia were categorized into the clinically improved and unimproved groups using the Chicago Chiari Outcome Scale. The imaging and clinical parameters were evaluated pre- and postoperatively.Results: This study included 25 patients of whom 19 (76.0%) had syringomyelia. At the 1-year follow-up, the syrinx diameter had decreased in 11 patients (57.8%). The increased TD significantly differed between the syrinx reduction and nonreduction groups. At the 1-year follow-up, 12 and seven patients with syringomyelia were categorized into the clinically improved and unimproved groups, respectively. The clinically improved and unimproved groups showed significant differences in the mean age and increased TD.Conclusions: Postoperative syrinx reduction was significantly correlated with the upward shifting of the cerebellar tonsil in patients with CMI. Our quantitative evaluation of the alterations in hindbrain position after FMD was easily performed and reflects the clinical outcomes.