Hidehiro Hirabayashi

Potential Use of Embryonic Stem Cells for the Treatment of Mouse Parkinsonian Models: Improved Behavior by Transplantation of In Vitro Differentiated Dopaminergic Neurons from Embryonic Stem Cells

Background and Aims. The purpose of the present study was to examine the efficacy of transplantation of mouse embryonic‐stem‐(ES)‐cell‐derived tyrosine hydroxylase‐positive (TH+) cells into Parkinsonian mice using behavioral tests and immunohistochemical evaluation.

A Quick and Universal Method for Stereotactic Visualization of the Subthalamic Nucleus before and after Implantation of Deep Brain Stimulation Electrodes

For deep brain stimulation (DBS) of the subthalamic nucleus (STN), it would be an advantage if the STN could be visualized with fast acquisition of MR images, allowing direct and individual targeting. We present a protocol for T2-weighted, nonvolumetric fast-acquisition MRI, implemented at 8 centers in 6 countries. Acquisition time varied between 3 min 5 s and 7 min 48 s according to the center, and imaging often provided visualization of the STN on axial and coronal scans. Postoperatively, the same imaging protocol permitted visualization of the target area and DBS electrodes with minimum artifacts. This imaging technique may contribute to a decrease in the number of electrode passes at surgery.

Stereotactic imaging of the pallidal target

In 48 consecutive patients, we applied a new stereotactic imaging technique to individually visualize the pallidal target before surgery. A turbo spin‐echo proton density sequence (acquisition time, 6 minutes 5 seconds) was used for 2‐mm‐thick contiguous axial scanning. Pallidocapsular border, medial putaminal border, and optic tract were visualized bilaterally in all patients. Boundaries of globus pallidus internus, globus pallidus externus, and lamina medullaris interna were clearly visualised in 71% of the patients. The anatomic target point was chosen in the middle of the visualized posteroventral pallidum, irrespective of the position of this point in relation to commissures. The lateralities of pallidocapsular border, lamina medullaris interna, and medial boundary of putamen were measured bilaterally in each patient, and the width of the posteroventral pallidum was assessed. The laterality of structures (measured from a point 2 mm anterior to midcommissural point and at a level 2–4 mm below anterior commissure–posterior commissure line) showed a wide range. The position of the pallidocapsular border varied by up to almost 1 cm between the most medial and the most lateral one. There were also variations in the position of the pallidal structures between left and right hemispheres in the same patients. The posteroventral pallidum was slightly more wide on the left than the right side. Given the significant inter‐ and intra‐individual variabilities of the position of pallidal structures, it may be hazardous to rely solely on the atlas and the commissures for targeting. A magnetic resonance imaging sequence that enables visualization in each individual patient of the target area and its surroundings may contribute to less electrode passes during intraoperative physiological exploration and to more exact location of the lesion or chronic electrode in the posteroventral pallidum.

Displacement of the facial nerve course by vestibular schwannoma: Preoperative visualization using diffusion tensor tractography

To preoperatively visualize the course of the facial nerve, which is displaced by vestibular schwannoma, using diffusion tensor (DT) tractography, and to evaluate the agreement with surgical findings.

Transplantation of embryonic stem cell-derived neural stem cells for spinal cord injury in adult mice

Abstract Aims: To investigate the efficacy of embryonic stem cell-derived neural stem cells (NSCs) for spinal cord injury (SCI) in mice and whether a combination treatment with thyroid hormone provides a more effective ES cell-based therapy. Methods: Nestin-positive NSCs were induced from undifferentiated mouse ES cells by a step-by-step culture and used as grafts. Thirty-six mice were subjected to an SCI at Th10 and divided into three groups of 12. Graft cells were transplanted into the injury site 10 days after injury. Group 1 mice were left under observation without receiving graft cells, while mice in Group 2 received 2 × 104 graft cells, and those in Group 3 received 2 × 104 graft cells and were treated with a continuous intraperitoneal injection of thyroxin using osmotic mini-pumps. Behavioral improvement was assessed by a scoring system throughout the experimental period until post-transplantation day (PD) 28. Results: Mice in Groups 2 and 3 demonstrated an improved behavioral function, as compared to those in Group 1 after PD 14. There was no significant difference in behavioral recovery between Groups 2 and 3. Conclusions: Transplantation of ES-NSCs into the injury site was effective for SCI, while thyroxine did not deliver additional effectiveness.

Is there a relationship between size and site of the stereotactic lesion and symptomatic results of pallidotomy and thalamotomy

Forty-six patients who had 50 stereotactic procedures (36 pallidotomies and 14 thalamotomies) were assessed clinically with regard to akinesia, tremor, dyskinesias and dystonias, and underwent a stereotactic imaging study 6 months after surgery. The surgical results were rated as excellent, good/fair or no change, respectively, for each symptom, and were correlated to the volume and location of the stereotactic lesion. The effect of pallidotomy on akinesia was moderate and correlated with a larger lesion volume. The positive effect of pallidotomy on dyskinesias, dystonia and tremor was more pronounced and unrelated to the size of the lesion. The effect of thalamotomy on tremor was also unrelated to the lesion volume. The location of the pallidal lesions correlated only with the effect on akinesia: the more posterior the lesion in the pallidum, the better the effect on this symptom. For thalamotomy, there was no relationship between lesion location and effect on tremor. It is concluded that improvement in akinesia following pallidotomy is more difficult to obtain than improvement of the other parkinsonian symptoms, and this improvement requires a larger lesion which is located very posterior in the ventral pallidum.

Expansive laminoplasty for multilevel cervical OPLL.

Expansive laminoplasty is a new technique for the management of cervical ossification of the posterior longitudinal ligament (OPLL). Twenty patients were followed up for an average 3-year period. Follow-up examinations were performed every 3 months and at 1-year intervals. On lateral radiographs, the average increase in the anteroposterior (AP) diameter of the canal was 42%. Bone fusion was documented on computed tomography (CT) studies 3 months after surgery in 96% of patients. An average 83% of normal range of motion was preserved on long-term follow-up (3 years on average). Postoperative improvement over the same interval increased from an average preoperative Japanese Orthopaedic Association score of 7.9 to 14.1 Expansive laminoplasty as described is safe and has a high fusion rate, while better preserving the normal range of motion.

Intraventricular transplantation of embryonic stem cell-derived neural stem cells in intracerebral hemorrhage rats

Abstract In the present study, we attempted to explore cell transplantation therapy for intracerebral hemorrhage (ICH) using embryonic stem (ES) cells. Collagenase-induced ICH rats were used as model animals. Mouse ES cells were differentiated into nestin-positive neural stem cells in vitro by alltrans retinoic acid (ATRA). ATRA-treated ES cells (105) were transplanted into the lateral ventricle in the hemisphere contralateral to the hemorrhage 7 days after collagenase infusion. Twenty-eight days after transplantation, ES-derived neurons and astrocytes were observed around the hematoma cavities of the brain in all of the ten rats receiving grafts. Graft-derived neurons were found in the subependymal area of the lateral ventricle as cellular nodules. Although one of the ten rats receiving grafts showed uncontrolled growth of astroglia derived from the ES cells, intraventricular transplantation of ATRA-treated ES cells is an effective delivery system of neuronal lineage-committed progenitor cells toward the site of ICH.

Treatment of Parkinson's disease model mice with allogeneic embryonic stem cells: necessity of immunosuppressive treatment for sustained improvement.

Abstract Objective: The purpose of the present study was to examine the efficacy of transplantation of mouse embryonic stem (ES) into Parkinsons disease (PD) model mice as well as the necessity of immunosuppression in allogeneic donor-host combinations. Materials and methods: ES cells, derived from SvJ129 strain mice, were differentiated into tyrosine hydroxylase (TH)-positive neurons in vitro by an embryoid body (EB)-based multistep differentiation method and used as graft cells for PD mice, which were prepared by injection of 6-hydroxydopamine (OHDA) into C57BL/6, BALB/c and C3H/HeN strains. Mice from each strain were divided into Groups 1–3. Four weeks after the 6-OHDA injection, Group 1 received phosphate-buffered saline in the striatum wounds, while Group 2 received 2 × 104 graft cells, and Group 3 mice received 2 × 104 graft cells and were also treated with cyclosporine A. Results: Apomorphine-induced rotational behavior was improved in Groups 2 and 3, but not in Group 1. However, the behavioral improvement ceased later in Group 2, whereas sustained improvement was observed in Group 3 throughout the 8 week observation period after transplantation. ES-derived TH+ cells were found at the grafted sites at the end of the experiment in Groups 2 and 3, and tended to be more abundant in Group 3. Conclusion: Intra-striatum transplantation of ES-derived dopaminergic neurons was effective in treating PD mice, even in allogeneic donor-host combinations. Immunosuppressive treatment did not have an effect on initial behavioral restoration after transplantation; however, it was necessary for sustained improvement over a prolonged period.

Comparison between Stereotactic CT and MRI Coordinates of Pallidal and Thalamic Targets using the Laitinen Noninvasive Stereoadapter

The coordinates of one and the same target were compared between stereotactic CT and MRI studies, using the original Laitinen noninvasive Stereoadapter, and a slightly modified stereoadapter in 34 patients scheduled for pallidotomy or thalamotomy. The differences between CT and MRI coordinates were significant for the anteroposterior y (p < 0.001) and the vertical z (p < 0.01) coordinates. When the targets were analyzed separately for the coordinates in the right and left hemispheres, only those of the left-sided targets were significantly different between CT and MRI measurements. In patients where a vertex support was added to the Stereoadapter, there were no differences between CT and MRI target coordinates, regardless of the side of the target. However, in all patient groups, the three-dimensional vectorial difference between CT and MRI coordinates showed that the MRI-defined targets lay anterior and dorsal, that is, rostral, to the CT-defined targets, with a 95% confidence interval of the differences ranging from 1.8 to 2.4 mm. This rostral shift in target coordinates on MRI versus CT happens to coincide with the usual approach of the probe towards the target during surgery. It is concluded that the differences in target coordinates in our study are due partly to MRI distortion and partly to repositioning error of the Stereoadapter on the head. The relatively low magnitude of these differences does not preclude the use of the Stereoadapter for MRI-guided functional stereotactic surgery, provided careful impedance monitoring and macrostimulation of the target area prior to lesioning.