Koichi Iwatsuki

Transplantation of olfactory mucosa following spinal cord injury promotes recovery in rats.

Several recent studies have demonstrated the potential therapeutic role of olfactory ensheathing cells in spinal cord injury. The aim of this study was to elucidate whether grafts of nasal olfactory mucosa containing olfactory ensheathing cells can repair the injured rat spinal cord as compared with the nasal respiratory mucosa containing no olfactory ensheathing cells. These grafts were then transplanted into the partially removed rat spinal cord. Compared with the respiratory mucosa-transplanted rats, the olfactory mucosa-transplanted rats partially recovered the movement of their hindlimbs and joints. Corticospinal tracing indicated that olfactory mucosa transplantation restored the severed tract. Therefore, olfactory mucosa has potential value in the repair of spinal cord injury.

Limited functional recovery in rats with complete spinal cord injury after transplantation of whole-layer olfactory mucosa: laboratory investigation.

OBJECT The olfactory mucosa (OM) consists of 2 layers, the epithelium and the lamina propria. Attempts have been made to restore motor function in rat models of spinal cord injury (SCI) by transplanting olfactory ensheathing cells from the lamina propria, but there has been no attempt to transplant the OM in animal models. To investigate the potential of the OM to restore motor function, the authors developed a rat model of SCI and delayed transplantation of syngenic OM. METHODS Two weeks after complete transection of the spinal cord at the T-10 level in Wistar rats, pieces of syngenic whole-layer OM were transplanted into the lesion. Rats that underwent respiratory mucosa transplantation were used as controls. The authors evaluated the locomotor activity according to the Basso-Beattie-Bresnahan scale for 8 weeks after transplantation. Obtained spinal cords were analyzed histologically. Results The OM transplantation rats showed significantly greater hindlimb locomotor recovery than the respiratory mucosa-transplanted rats. However, the recovery was limited according to the Basso-Beattie-Bresnahan scale. In the histological examination, the serotonergic raphespinal tract was regenerated. The pseudocyst cavity volume in the vicinity of the SCI lesion correlated negatively with the functional recovery. CONCLUSIONS Transplantation of whole-layer OM in rats contributes to functional recovery from SCI, but the effect is limited. In addition to OM transplantation, other means would be necessary for better outcomes in clinical situations.

Implantation of a Reservoir for Refractory Chronic Subdural Hematoma

OBJECTIVERecurrence of chronic subdural hematoma is not rare. Among patients who experience recurrence, severe background disease may adversely influence the prognosis of chronic subdural hematoma. We treated patients with these refractory hematomas with an Ommaya cerebrospinal fluid (CSF) reservoir and analyzed the effectiveness of the treatment. METHODSSixteen patients with refractory chronic subdural hematoma were studied. These patients had severe diseases that adversely influenced the clinical course of chronic subdural hematoma, including cerebral infarction, liver cirrhosis, thrombocytopenia, severe Parkinsonism, severe heart disease, psychiatric disease, and spinocerebellar degeneration. All patients were treated initially in the standard fashion: evacuation of the hematoma followed by irrigation and drainage of the hematoma cavity. In each patient, an Ommaya CSF reservoir was implanted after the hematoma recurred. Whenever the volume of the hematoma either decreased very slowly or increased, the reservoir was punctured. RESULTSThe hematoma size decreased to less than 3 mm a median of 60 days after introduction of the reservoir. Postoperatively, 13 patients returned to their condition before the onset of hematoma. One patient died of myocardial infarction, and two patients with Parkinson’s disease could not maintain their previous functional level; both remained in a partially dependent state. Complications consisted of minor bleeding in two patients and occlusion of the reservoir in two other patients. CONCLUSIONBy use of this method, reoperation was avoided and the patients were mobile early in the postoperative period. This method was suitable for refractory chronic subdural hematoma accompanied by severe disease that adversely influenced the clinical course.

Isthmus-guided Cortical Bone Trajectory for Pedicle Screw Insertion

Herein is described cortical bone trajectory (CBT), a new path for pedicle screw insertion for lumbar vertebral fusion. Because the points of insertion are under the end of the inferior articular process, and because the screws are inserted toward the lateral side, there is less soft tissue development than with the conventional technique; the CBT technique therefore enables less invasive surgery than the conventional technique. However, it has some drawbacks. For example, in the original CBT approach, the points of insertion are in the vicinity of the end of the inferior articular process. Because this joint has been destroyed in many patients who have indications for intervertebral fusion surgery, it is sometimes difficult to use it as a reference point for screw insertion location. With severe lateral slippage, the screw insertion site can become significantly dislocated sideways, with possible resultant damaging to the spinal canal and/or nerve root. The CBT technique here involved inserting the screws while keeping clear of the intervertebral foramen with the assistance of side view X‐ray fluoroscopy and using the end of the inferior articular process and the isthmus as points of reference for screw location.

Bow hunter’s stroke due to instability at the uncovertebral C3/4 joint

Bow hunter’s stroke is typically due to mechanical compression or stretching of the dominant vertebral artery (VA) during contralateral head rotation against the bony elements of the atlas and axis. We report a case of vertebrobasilar insufficiency due to bilateral vertebral artery occlusion at the left C3–4 and the right C1–2 junction on rightward head rotation. A 64-year-old man experienced ischemic symptoms during 90° head rotation to the right with complete resolution of symptoms after returning his head to the neutral position. Dynamic cervical angiography with rightward head rotation showed severe compression of the right VA at the transverse foramen of C3–4 and mechanical stenosis of the left VA at the C1–2 level. During head rotation, the flow of the right VA was decreased more than the left side. Cervical 3-D computed tomography (CT) on rightward head rotation demonstrated displacement of the uncovertebral C3–4 joint, with excessive rotation of the C3 vertebral body. Based on these findings, instability at C3–4 was suspected to be the main cause of the vertebrobasilar insufficiency. Anterior discectomy and fusion at the C3/4 level were performed. Postoperatively, the patient experienced complete resolution of symptoms, and dynamic cervical angiography showed disappearance of the compression of the right VA. To our knowledge, this is the first reported case of bow hunter’s stroke diagnosed by dynamic cerebral angiography and cervical 3-D CT without angiography, and treated by anterior decompression and fusion without decompression of the VA.

Increase in plasma nitric oxide end products following rat cortical injury

The changes in plasma nitric oxide (NO) end products, nitrite (NO2-) and nitrate (NO3-), were studied following cortical injury in rats. At 3 days after stereotactic cortical injury (day 3), plasma NO end products were significantly increased (P < 0.01), and decreased by day 7. This increase on day 3 was inhibited by a selective inhibitor of inducible NO synthase (NOS), aminoguanidine (100 mg/kg, i.p. on days 1 and 2, P < 0.001). The present study first demonstrated the temporary increase in plasma NO end products, which is attributable to the inducible NOS activation after cerebral injury.

Adult olfactory sphere cells are a source of oligodendrocyte and Schwann cell progenitors

The olfactory epithelial layer contains multipotent horizontal basal cells (HBCs) that differentiate into olfactory sensory neurons. Here, we show that rat HBCs express oligodendrocyte progenitor cell (OPC) and astrocyte markers. We generated olfactory sphere (OS) cells in cultures that were derived from adult rat olfactory mucosa. Fluorescence-activated cell sorting and immunofluorescence analyses showed that OS cells also express OPC and astrocyte markers. Interestingly, OS cells underwent oligodendrocyte differentiation in vitro. To study oligodendrocyte differentiation in vivo, OS cells were transplanted into injured rat spinal cords. The transplanted cells integrated into host tissue and differentiated into oligodendrocytes. When transected saphenous nerve ends were encased in collagen-containing silicone tubes with or without OS cells, the transplanted OS cells differentiated into Schwann cells. Our data provide new insights into of the stemness of OS cells.

Intranasal delivery of bone marrow stromal cells to spinal cord lesions

OBJECT The intranasal delivery of bone marrow stromal cells (BMSCs) or mesenchymal stem cells to the injured brains of rodents has been previously reported. In this study, the authors investigated whether BMSCs migrate to spinal cord lesions through an intranasal route and whether the administration affected functional recovery. METHODS Forty Sprague-Dawley rats that were subjected to spinal cord injuries at the T7-8 level were divided into 5 groups (injured + intranasal BMSC-treated group, injured + intrathecal BMSC-treated group, injured-only group, injured + intranasal vehicle-treated group, and injured + intrathecal vehicle-treated group). The Basso-Beattie-Bresnahan (BBB) scale was used to assess hind limb motor functional recovery for 2 or 4 weeks. Intralesionally migrated BMSCs were examined histologically and counted at 2 and 4 weeks. To evaluate the neuroprotective and trophic effects of BMSCs, the relative volume of the lesion cavity was measured at 4 weeks. In addition, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) levels in the CSF were evaluated at 2 weeks. RESULTS Intranasally administered BMSCs were confirmed within spinal cord sections at both 2 and 4 weeks. The highest number, which was detected in the intrathecal BMSC-treated group at 2 weeks, was significantly higher than that in all the other groups. The BBB score of the intranasal BMSC-treated group showed statistically significant improvements by 1 week compared with the control group. However, in the final BBB scores, there was a statistically significant difference only between the intrathecal BMSC-treated group and the control group. The cavity ratios in the BMSC-treated groups were smaller than those of the control groups, but the authors did not find any significant differences in the NGF and BDNF levels in the CSF among the treatment and control groups. CONCLUSIONS BMSCs reached the injured spinal cord through the intranasal route and contributed to the recovery of hind limb motor function and lesion cavity reduction. However, the effects were not as significant as those seen in the intrathecal BMSC-treated group.

A new three-dimensional axonal outgrowth assay for central nervous system regeneration.

Although recent studies have shown that cell transplantation is effective in promoting regeneration of the central nervous system (CNS) of adult mammals, functional recovery has been reported to be limited. In vitro models of axonal outgrowth assays are often used as easy methods for screening cells for transplantation but often fail to reflect the physiological conditions of in vivo CNS injury models. In order to bridge the gap between in vitro and in vivo models, we have established a new organotypic co-culture system comprising cortical tissue and a Matrigel containing several cell types that are candidates for transplantation therapy for CNS injury. In this model, cells transplanted in a Matrigel produce a three-dimensional architecture, with axons elongating from the cortex in the Matrigel. The ability of the transplanted cells to promote axonal growth was examined quantitatively by assessing axonal number and length. Moreover, we observed site-specific rearrangement of transplanted cells and interactions between axons and cells, including several cortical cells that migrated into the gel. These results indicate that our co-culture system can provide a useful assay for transplanted cells prior to in vivo screening.

Intradural cervical lipoma with parenchymal marginal fibrous tissue : Case report

OBJECTIVE The author reports an intradural cervical subpial lipoma with parenchymal marginal fibrous tissue causing neurological deterioration. METHODS Computed tomographic and magnetic resonance imaging scans revealed the lesion. Magnetic resonance imaging fat suppression was an especially useful tool for diagnosis. RESULTS The gross appearance and microscopic findings implied that this tumor had a progressive character. A subtotal resection was carried out and pathological studies confirmed the diagnosis. CONCLUSION Postoperatively, the patient made an excellent recovery.