Teriparatide improves volumetric bone mineral density and fine bone structure in the UIV+1 vertebra, and reduces bone failure type PJK after surgery for adult spinal deformity.

We conducted a prospective comparative study of the effect of teriparatide therapy for preventing vertebral-failure-type PJK after reconstructive surgery for adult spinal deformity. Prophylactic teriparatide improved the volumetric bone mineral density and fine bone structure of the vertebra above the upper-instrumented vertebra and reduced the incidence of vertebral-failure-type PJK. INTRODUCTION: Proximal junctional kyphosis (PJK) is a complication after corrective surgery for spinal deformity. This study sought to determine whether teriparatide (TP) is an effective prophylactic against PJK type 2 (vertebral fracture) in surgically treated patients with adult spinal deformity (ASD). METHODS: Forty-three patients who started TP therapy immediately after surgery and 33 patients who did not receive TP were enrolled in this prospective case series. These patients were female, over 50, surgically treated for ASD, and followed for at least 2 years. Preoperative and postoperative standing whole-spine X-rays and dual-energy X-ray absorptiometry scans, and multidetector CT images obtained before and 6 months after surgery were used to analyze the bone strength in the vertebra above the upper-instrumented vertebra (UIV+1). RESULTS: Mean age was 67.9 years. After 6 months of treatment, mean hip-bone mineral density (BMD) increased from 0.721 to 0.771 g/cm2 in the TP group and decreased from 0.759 to 0.729 g/cm2 in the control group. This percent BMD change between groups was significant (p < 0.05). The volumetric BMD (326 to 366 mg/cm3) and bone mineral content (BMC) (553 to 622 mg) at UIV+1 were also significantly increased in TP group. The bone volume/tissue volume ratio increased from 46 to 54 % in the TP group, and the trabecular bone thickness and number increased by 14 and 5 %, respectively. At the 2-year follow-up, the PJK type 2 incidence was significantly lower in the TP group (4.6 %) than in the control group (15.2 %; p = .02). CONCLUSIONS: Prophylactic TP treatment improved the volumetric BMD and fine bone structure at UIV+1 and reduced the PJK-type 2 incidence.

Increase of oligodendrocyte progenitor cells after spinal cord injury.

The reaction of oligodendrocyte progenitor cells (OPCs) after spinal cord injury (SCI) is poorly understood. In this study, we examined oligodendroglial reactions after contusion SCI in adult rats by immunohistochemistry. OPCs were identified by staining with monoclonal antibodies (mAbs) A2B5 and O4. Each of the A2B5-, O4-positive OPCs and galactocerebroside-positive oligodendrocytes dramatically increased in the lesion of the dorsal posterior funiculus. Bromodeoxyuridine (BrdU) incorporation studies showed that most O4-positive cells in the lesion were labeled with BrdU, suggesting that these OPCs were proliferative. In contrast, the expression of myelin basic protein was decreased in the lesion compared with controls that received laminectomy only. From the injured cord, OPCs were isolated by immunopanning with mAb A2B5. We observed an increased number of OPCs from the injured spinal cords compared with those isolated from controls and unoperated animals. After several days in culture, the OPCs from the lesion expressed galactocerebroside. These results suggest that OPCs are induced and can differentiate following SCI in the adult rat.

Experimental study on MRI evaluation of the course of cervical spinal cord injury.

STUDY DESIGN: An experimental study was conducted to evaluate MRI signal changes within the spinal cord after the injury in rats. OBJECTIVES: To clarify the significance of MRI signal changes in the injured cervical cord. SETTING: Tokyo, Japan. METHODS: Cervical spinal cord injury was produced in rats by placing a 20-g, or 35-g weight on exposed dura at the C6 level for 5 min (20 g- or 35 g-compression group). Motor function was evaluated by the inclined-plane method at 2, 7 and 28 days after the injury. T1- and T2-weighted images were produced by the spin-echo method with a static magnetic field strength of 2.0 tesla, at 2 and 28 days after the injury, and then the histopathological examinations were performed. RESULTS: In the 20-g compression group, which recovered from the paralysis at 28 days, MR images were T1 iso signal/T2 high signal 2 days after the injury and T1 iso signal/T2 high signal after 28 days. The changes in MRI signal 2 and 28 days represented edema and gliosis, respectively. In the 35-g compression group, which incompletely recovered from paralysis at 28 days. MR images were T1 iso-signal/T2 low signal surrounded by high signal 2 days after the injury and T1 low/T2 high signal at 28 days. The MRI signal changes 2 and 28 days reflected hemorrhage with edema and cavities, respectively. CONCLUSION: T2 low signal of the spinal cord observed early after injury reflects hemorrhage and may serve as an indicator of a poor prognosis. T1 low/T2 high signals from the subacute to chronic period indicated persistence of paralysis and limited recovery of function.

Changes of amino acid levels and aspartate distribution in the cervical spinal cord after traumatic spinal cord injury.

To evaluate the role of excitatory amino acids in secondary injury occurring after spinal cord trauma, several experimental studies focusing on the the changes of amino acid levels in the spinal cord have been performed to date. However, because of technical limitations, it has not been possible to correlate the local changes of excitatory amino acids with the total tissue levels of excitatory amino acids. To investigate the connection between the spread of injury and the excitatory amino acids, we assessed, the local changes of aspartate through novel experimental approaches like immunoreactivity via fluorescence microphotometry and histopathology while also analyzing the total tissue levels of amino acids via HPLC. These studies were performed using a model of incomplete cervical spinal cord injury in rats. Through this approach, we found that the levels of excitatory amino acids, such as glutamate and aspartate, began to decrease immediately after injury. No significant decrease was observed in the other amino acids. Similarly, local changes in aspartate in the spinal cord were observed using fluorescence microphotometry. The decrease in the anterior and posterior horns was rapid up to 15 min after injury, but, slowed thereafter, suggesting that a release of excitatory amino acids occurred at the site of primary injury almost immediately following injury. At 15-min post-injury large neurons within the injured cord appeared intact on histopathological analysis demonstrating that the alteration of excitatory amino acids occurs prior to histopathological change. Histopathological change in the white matter occurred more slowly than in the anterior and posterior horns, suggesting the spread of the lesion by secondary damage due to an autoclastic mechanism.

Decreased choline acetyltransferase activity in the murine spinal cord motoneurons under chronic mechanical compression.

The tiptoe-walking Yoshimura (twy) mouse is a model of chronic spinal cord compression caused by ossification of intraspinal ligaments. Choline acetyltransferase (CAT), which is known to be a specific marker of cholinergic neurons, best reflects spinal motoneuron function. Changes in CAT immunoreactivity following chronic spinal cord compression in twy mice were investigated quantitatively in order to elucidate spinal motoneuron functional changes according to the degree and direction of compression. Thirty 24-week-old twy mice were used in this study. They were divided into three groups according to the direction of spinal cord compression (anterior, posterior, and lateral) and the CAT immunoreactivities in whole sections of their upper cervical spinal cords were investigated quantitatively using a fluorescence microphotometry system. The lateral compression group showed histological spinal motoneuron atrophy and loss on the compressed, but not the non-compressed, side. Spinal motoneuron atrophy and loss were observed when the severity of spinal canal stenosis due to the ossified lesion, expressed as the occupation rate, was 30% or more, but the spinal motoneurons appeared normal when it was below 30%. The CAT immunofluorescence intensity of the anterior horn showed a linear negative correlation with the degree of canal stenosis. When the occupation rate was below 20%, the CAT immunofluorescence intensities in the anterior horns of the compression and control groups did not differ significantly. The CAT immunofluorescence intensity of twy mice with occupation rates of 20% or more were significantly lower than that of those with occupation rates below 20%. Furthermore, the CAT immunofluorescence intensity was significantly lower on the compressed than the non-compressed side of the lateral compression group. Thus, our findings indicate that an occupation rate of about 20% may be the critical level for functional changes in the spinal motoneurons.

Muscle reorganization following incomplete cervical spinal cord injury in rats.

This study on rats was designed to evaluate the change of biceps muscle fibers by enzyme histochemical examination and the change of distribution of motoneurons innervating biceps muscle fibers by retrograde tracer examination after incomplete spinal cord injury. Incomplete spinal cord injury was produced by placing a 20 g weight on exposed dura at the C6 level. The number of the labeled motoneurons of C6 segment significantly decreased compared with that in the control, but there were no significant changes in the other segments at 4 weeks after the injury. Moreover, there was type grouping of biceps muscle fibers at 4 weeks after the injury. These findings indicated that the incomplete cervical spinal cord injury at C6 level in rats caused the partial denervation and then reinnervation of biceps muscle fibers by the collateral sprouting of the remaining motoneurons which belonged to the same motoneuron pool of the injured motoneurons.

Changes in choline acetyltransferase activity and distribution following incomplete cervical spinal cord injury in the rat.

Incomplete cervical spinal cord injuries were produced in rats by placing 10 g or 20 g weight on exposed dura at the C6 level for 5 min (Mild or Moderate injury). These two degrees of the injury resulted in initial motor functional deficits, followed by recoveries. In this study, changes in choline acetyltransferase activity and distribution following the incomplete cervical cord injuries were investigated using radioenzyme assay, and fluorescence microphotometry. We demonstrated that mild injury led to a transient decrease of choline acetyltransferase activity in the compressed spinal cord segment, but showed almost no histologic change at two days after injury. Although a low level of choline acetyltransferase immunofluorescence was found in the ventrolateral anterior horn at two days after injury, it recovered completely by one week after injury. These findings suggest that there was a strong correlation between the transient motor functional deficit and the decrease in choline acetyltransferase activity following mild injury. Moderate injury resulted in persistent low level of choline acetyltransferase activity in the compressed spinal cord segment accompanied by a striking loss of gray matter. On the other hand, at seven, 14 and 28 days after injury, over-expression of choline acetyltransferase activity was found in the neighboring spinal cord segments located both rostral and caudal to the injury, which showed no histologic change. In addition, excessively high levels of choline acetyltransferase immunofluorescence were found in the ventrolateral anterior horn of these segments. A strong correlation was found between the motor functional recovery and the late, excessive high levels of choline acetyltransferase activity in the neighboring regions. These results suggest that cholinergic neurons, especially spinal motor neurons may play an important role in the motor functional recovery following incomplete cervical spinal cord injury.

Changes in choline acetyltransferase distribution in the cervical spinal cord after reversible cervical spinal cord injury.

Reversible spinal cord injury (SCI) at C6 level in rats, produced by the weight-placed method, resulted in a severe motor functional deficit initially, followed by a gradual recovery. During the recovery, choline acetyltransferase (CAT) distribution in the cervical spinal cord was investigated at 2, 4, 7, 14 and 28 days after the injury by quantitative immunohistochemistry with a fluorescence microphotometry system. At C6 level, the fluorescence intensity of the ventrolateral anterior horn (VLAH), which reflected the concentration of CAT, decreased to approximately 50% of that of the sham-operated group at 2 days. It then recovered to 60% at 4 days after the injury, and remained unchanged thereafter. Fluorescence intensities in VLAH at C4-5 and C7-8 levels decreased to approximately 60-70% at 2 days after the injury, but it recovered and increased to 110-130% thereafter.