The aims of our study are to evaluate the effect of curcumin on spinal cord neural progenitor cell (SC-NPC) proliferation and to clarify the mechanisms of mitogen-activated protein (MAP) kinase signaling pathways in SC-NPCs.
We established cultures of SC-NPCs, extracted from the spinal cord of Sprague-Dawley rats weighing 250 g to 350 g. We measured proliferation rates of SC-NPCs after curcumin treatment at different dosage. The immuno-blotting method was used to evaluate the MAP kinase signaling protein that contains extracellular signal-regulated kinases (ERKs), p38, c-Jun NH2-terminal kinases (JNKs) and β-actin as the control group.
Curcumin has a biphasic effect on SC-NPC proliferation. Lower dosage (0.1, 0.5, 1 µM) of curcumin increased SC-NPC proliferation. However, higher dosage decreased SC-NPC proliferation. Also, curcumin stimulates proliferation of SC-NPCs via the MAP kinase signaling pathway, especially involving the p-ERK and p-38 protein. The p-ERK protein and p38 protein levels varied depending on curcumin dosage (0.5 and 1 µM, p<0.05).
Curcumin can stimulate proliferation of SC-NPCs via ERKs and the p38 signaling pathway in low concentrations.
Curcumin; Spinal cord neural progenitor cell; Mitogen activated protein kinase
Although curcumin has a protective effect on bone remodeling, appropriate therapeutic concentrations of curcumin are not well known as therapeutic drugs for osteoporosis. The purpose of this study was to compare the bone sparing effect of treatment of low-dose and high-dose curcumin after ovariectomy in rats.
Forty female Sprague-Dawley rats underwent either a sham operation (the sham group) or bilateral ovariectomy (OVX). The ovariectomized animals were randomly distributed among three groups; untreated OVX group, low-dose (10 mg/kg) curcumin administered group, and high-dose (50 mg/kg) curcumin group. At 4 and 8 weeks after surgery, serum biochemical markers of bone turnover were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae were determined by micro-computed tomography (CT). In addition, mechanical strength was determined by a three-point bending test.
High-dose curcumin group showed significantly lower osteocalcin, alkaline phosphatase, and the telopeptide fragment of type I collagen C-terminus concentration at 4 and 8 weeks compared with the untreated OVX group as well as low-dose curcumin group. In the analyses of micro-CT scans of 4th lumbar vertebrae, the high-dose curcumin treated group showed a significant increase in bone mineral densities (p=0.028) and cortical bone mineral densities (p=0.036) compared with the low-dose curcumin treated group. Only high-dose curcumin treated group had a significant increase of mechanical strength compared with the untreated OVX group (p=0.015).
The present study results demonstrat that a high-dose curcumin has therapeutic advantages over a low-dose curcumin of an antiresorptive effect on bone remodeling and improving bone mechanical strength.
Curcumin; Micro-computed tomography; Osteoporosis; Ovariectomy; Rat
Lumbar microdiscectomy (MD) is the gold standard for treatment of lumbar disc herniation. Generally, the surgeon attempts to protect the facet joint in hopes of avoiding postoperative pain/instability and secondary degenerative arthropathy. We believe that preserving the facet joint is especially important in young patients, owing to their life expectancy and activity. However, preserving the facet joint is not easy during lumbar MD. We propose several technical tips (superolateral extension of conventional laminotomy, oblique drilling for laminotomy, and additional foraminotomy) for facet joint preservation during lumbar MD.
Lumbar disc herniation; Microdiscectomy; Facet joint; Laminotomy; Foraminotomy
It remains debatable whether cervical spine fusion cages should be filled with any kind of bone or bone substitute. Cortical and subcortical bone from the anterior and posterior osteophytes of the segment could be used to fill the cage. The purposes of the present study are to evaluate the clinical outcomes and radiological outcomes including bone fusion and subsidence that occurred after anterior cervical discectomy and fusion using a stand-alone cage packed with local autobone graft.
Thirty-one patients who underwent anterior cervical fusion using a stand-alone polyetheretherketone (PEEK) cage packed with local autobone graft from July 2009 to december 2011 were enrolled in this study. Bone fusion was assessed by cervical plain radiographs and computed tomographic scan. Nonunion was evaluated according to the absence of bony bridge on computed tomographic scan. Subsidence was defined as a ≥2 mm decrease of the interbody height at the final follow-up compared to that measured at the immediate postoperative period.
Subsidence was observed in 7 patients (22.6%). Of 7 patients with subsidence greater 2 mm, nonunion was developed in 3. Three patients with subsidence greater 2 mm were related with endplate damage during intraoperative endplate preparation. Solid bone fusion was achieved in 28 out of 31 patients (90.3%).
With proper patient selection and careful endplate preparation, anterior cervical discectomy and fusion (ACDF) using a stand-alone PEEK cage packed with local autobone graft could be a good alternative to the standard ACDF techniques with plating.
Cage; Cervical spine; Discectomy; Local bone
We report a case of 29-year-old man diagnosed as a primary eosinophilic granuloma (EG) lesion of the seventh cervical vertebra. He had paresthesia on both arms, and grasping weakness for 10 days. Cervical magnetic resonance image (MRI) showed an enhancing mass with ventral epidural bulging and cord compression on the seventh cervical vertebra. Additionally, we performed spine series MRI, bone scan and positive emission tomography for confirmation of other bone lesions. These studies showed no other pathological lesions. He underwent anterior cervical corpectomy of the seventh cervical vertebra and plate fixation with iliac bone graft. After surgical management, neurological symptoms were much improved. Histopathologic evaluation confirmed the diagnosis of EG. There was no evidence of tumor recurrence at 12 months postoperative cervical MRI follow-up. We reported symptomatic primary EG of cervical spine successfully treated with surgical resection.
Eosinophilic granuloma; Adult cervical tumor; Surgical approach
This study investigates the effect of valproic acid (VPA) on expression of neural stem/progenitor cells (NSPCs) in a rat spinal cord injury (SCI) model.
Adult male rats (n=24) were randomly and blindly allocated into three groups. Laminectomy at T9 was performed in all three groups. In group 1 (sham), only laminectomy was performed. In group 2 (SCI-VPA), the animals received a dose of 200 mg/kg of VPA. In group 3 (SCI-saline), animals received 1.0 mL of the saline vehicle solution. A modified aneurysm clip with a closing force of 30 grams was applied extradurally around the spinal cord at T9, and then rapidly released with cord compression persisting for 2 minutes. The rats were sacrificed and the spinal cord were collected one week after SCI. Immunohistochemistry (IHC) and western blotting sample were obtained from 5 mm rostral region to the lesion and prepared. We analyzed the nestin immunoreactivity from the white matter of ventral cord and the ependyma of central canal. Nestin and SOX2 were used for markers for NSPCs and analyzed by IHC and western blotting, respectively.
Nestin and SOX2 were expressed significantly in the SCI groups but not in the sham group. Comparing SCI groups, nestin and SOX2 expression were much stronger in SCI-VPA group than in SCI-saline group.
Nestin and SOX2 as markers for NSPCs showed increased expression in SCI-VPA group in comparison with SCI-saline group. This result suggests VPA increases expression of spinal NSPCs in SCI.
Neural stem/progenitor cell; Spinal cord injury; Valproic acid; Nestin; SOX2
To evaluate the effect of calcium supplementation on spinal bone fusion in ovariectomized (OVX) rats.
Sixteen female Sprague Dawley rats underwent bilateral ovariectomy at 12 weeks of age to induce osteoporosis and were randomly assigned to two groups : control group (n=8) and calcium-supplemented group (OVX-Ca, n=8). Autologous spinal bone fusion surgery was performed on both groups 8 weeks later. After fusion surgery, the OVX-Ca group was supplemented with calcium in drinking water for 8 weeks. Blood was obtained 4 and 8 weeks after fusion surgery. Eight weeks after fusion surgery, the rats were euthanized and the L4-5 spine removed. Bone fusion status and fusion volume were evaluated by manual palpation and three-dimensional computed tomography.
The mean fusion volume in the L4-5 spine was significantly greater in the OVX-Ca group (71.80±8.06 mm3) than in controls (35.34±8.24 mm3) (p<0.01). The level of osteocalcin, a bone formation marker, was higher in OVX-Ca rats than in controls 4 weeks (610.08±10.41 vs. 551.61±12.34 ng/mL) and 8 weeks (552.05±19.67 vs. 502.98±22.76 ng/mL) after fusion surgery (p<0.05). The level of C-terminal telopeptide fragment of type I collagen, a bone resorption marker, was significantly lower in OVX-Ca rats than in controls 4 weeks (77.07±12.57 vs. 101.75±7.20 ng/mL) and 8 weeks (69.58±2.45 vs. 77.15±4.10 ng/mL) after fusion surgery (p<0.05). A mechanical strength test showed that the L4-5 vertebrae in the OVX-Ca group withstood a 50% higher maximal load compared with the controls (p<0.01).
Dietary calcium given to OVX rats after lumbar fusion surgery improved fusion volume and mechanical strength in an ovariectomized rat model.
Osteoporosis; Ovariectomized rat; Calcium; Spinal bone fusion
Conventional laminectomy is the most popular technique for the complete removal of intradural spinal tumors. In particular, the central portion intramedullary tumor and large intradural extramedullary tumor often require a total laminectomy for the midline myelotomy, sufficient decompression, and adequate visualization. However, this technique has the disadvantages of a wide incision, extensive periosteal muscle dissection, and bony structural injury. Recently, split-spinous laminectomy and tubular retractor systems were found to decrease postoperative muscle injuries, skin incision size and discomfort. The combined technique of split-spinous laminectomy, using a quadrant tube retractor system allows for an excellent exposure of the tumor with minimal trauma of the surrounding tissue. We propose that this technique offers possible advantages over the traditional open tumor removal of the intradural spinal cord tumors, which covers one or two cervical levels and requires a total laminectomy.
Cervical cord tumor; Split-spinous laminectomy; Quadrant tube retractor
The purpose of this study was to evaluate the different patterns of bone loss between the lumbar spine and the femur after ovariectomy in rats.
Twenty-four female Sprague-Dawley rats underwent a sham operation (the sham group) or bilateral ovariectomy (the ovariectomized group). Four and eight weeks after operation, six rats from each of the two groups were euthanized. Serum biochemical markers of bone turnover including osteocalcin and alkaline phosphatase (ALP), which are sensitive biochemical markers of bone formation, and the telopeptide fragment of type I collagen C-terminus (CTX), which is a sensitive biochemical marker of bone resorption, were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae and femur were determined by micro-computed tomography.
Ovariectomized rats were found to have higher osteocalcin, ALP and CTX levels than sham controls. Additionally, 8 weeks after ovariectomy in the OVX group, serum levels of osteocalcin, ALP and CTX were significantly higher than those of 4 weeks after ovariectomy. Bone loss after ovariectomy was more extensive in the 4th lumbar spine compared to the femur. Bone loss in the 4th lumbar spine was mainly caused by trabecular thinning, but in the femur, it was mainly caused by trabecular elimination.
The present study demonstrates different patterns of bone loss between the 4th lumbar spine and the femur in ovariectomized rats. Therefore, when considering animal models of osteoporosis, it is important that bone sites should be taken into account.
Bone loss; Micro-CT; Osteoporosis; Ovariectomy; Rat
The purpose of this study was to verify the appropriateness of ovariectomized rats as the osteoporosis animal model.
Twelve female Sprague-Dawley rats underwent a sham operation (the sham group) or bilateral ovariectomy [the ovariectomy (OVX) group]. Eight weeks after operations, serum biochemical markers of bone turnover were analyzed; osteocalcin and alkaline phosphatase, which are sensitive biochemical markers of bone formation, and C-terminal telopeptide fragment of type I collagen C-terminus (CTX), which is a sensitive biochemical marker of bone resorption. Bone histomorphometric parameters and microarchitectural properties of 4th lumbar vertebrae were determined by micro-computed tomographic (CT) scan.
The OVX group showed on average 75.4% higher osteocalcin and 72.5% higher CTX levels than the sham group, indicating increased bone turnover. Micro-CT analysis showed significantly lower bone mineral density (BMD) (p=0.005) and cortical BMD (p=0.021) in the OVX group. Furthermore, the OVX group was found to have a significantly lower trabecular bone volume fraction (p=0.002).
Our results showed that bone turnover was significantly increased and bone mass was significantly decreased 8 weeks after ovariectomy in rats. Thus, we propose that the ovariectomized rat model be considered a reproducible and reliable model of osteoporosis.
Bone loss; Bone turnover; Osteoporosis; Ovariectomy; Rat
Hemorrhagic complications associated with aspirin use occur primarily at skin or gastrointestinal sites but can occasionally occur in the central nervous system. In particular, spontaneous spinal epidural hemorrhage (SSEH) associated with aspirin is very rare. We report a case of low-dose (100 mg daily) aspirin-related SSEH that was successfully treated with medical management. Our case indicates that low-dose aspirin could induce SSEH and that conservative treatment with close observation and repeated imaging studies should be considered in cases with neurological improvement or mild deficits.
Aspirin; Spinal epidural hematoma; Medical management
Valproic acid (VPA), as known as histone deacetylase inhibitor, has neuroprotective effects. This study investigated the histological changes and functional recovery from spinal cord injury (SCI) associated with VPA treatment in a rat model.
Locomotor function was assessed according to the Basso-Beattie-Bresnahan scale for 2 weeks in rats after receiving twice daily intraperitoneal injections of 200 mg/kg VPA or the equivalent volume of normal saline for 7 days following SCI. The injured spinal cord was then examined histologically, including quantification of cavitation.
Basso-Beattie-Bresnahan scale scores in rats receiving VPA were significantly higher than in the saline group (p<0.05). The cavity volume in the VPA group was significantly reduced compared with the control (saline-injected) group (p<0.05). The level of histone acetylation recovered in the VPA group, while it was significantly decreased in the control rats (p<0.05). The macrophage level was significantly decreased in the VPA group (p<0.05).
VPA influences the restoration of hyperacetylation and reduction of the inflammatory reaction resulting from SCI, and is effective for histology and motor function recovery.
Valproic acid; Spinal cord injury; Clip compression model; Acetylation; HDAC inhibitor
We investigated the neuroprotective effect of anthocyanin, oxygen radical scavenger extracted from raspberries, after traumatic spinal cord injury (SCI) in rats.
The animals were divided into two groups : the vehicle-treated group (control group, n=20) received an oral administration of normal saline via stomach intubation immediately after SCI, and the anthocyanin-treated group (AT group, n=20) received 400 mg/kg of cyanidin 3-O-β-glucoside (C3G) in the same way. We compared the neurological functions, superoxide expressions and lesion volumes in two groups.
At 14 days after SCI, the AT group showed significant improvement of the BBB score by 16.7±3.4%, platform hang by 40.0±9.1% and hind foot bar grab by 30.8±8.4% (p<0.05 in all outcomes). The degree of superoxide expression, represented by the ratio of red fluorescence intensity, was significantly lower in the AT group (0.98±0.38) than the control group (1.34±0.24) (p<0.05). The lesion volume in lesion periphery was 32.1±2.4 µL in the control and 24.5±2.3 µL in the AT group, respectively (p<0.05), and the motor neuron cell number of the anterior horn in lesion periphery was 8.3±5.1 cells/HPF in the control and 13.4±6.3 cells/HPF in the AT group, respectively (p<0.05).
Anthocyanin seemed to reduce lesion volume and neuronal loss by its antioxidant effect and these resulted in improved functional recovery.
Spinal cord trauma; Anthocyanin; Antioxidants
Lumbar spinal stenosis (LSS) is a common spinal disease in the elderly. The cardinal symptom of LSS is neurogenic claudication, but not all patients present with such typical symptom. The clinical symptoms are often confused with symptoms of peripheral neuropathy, musculo-skeletal disease and other medical conditions in elderly patients. In particular, LSS presenting with rapid progression of leg weakness must be distinguished from other combined diseases. We report a case of rapid progressive leg weakness in a patient with LSS and iatrogenic adrenal insufficiency that was induced by obscure health supplement.
Leg weakness; Lumbar spinal stenosis; Adrenal insufficiency
We report a case of pedicle screw loosening treated by modified transpedicular screw augmentation technique using polymethylmethacrylate (PMMA), which used the anchoring effect of hardened PMMA. A 56-year-old man who had an L3/4/5 fusion operation 3 years ago complained of continuous low back pain after this operation. The computerized tomography showed a radiolucent halo around the pedicle screw at L5. We augmented the L5 pedicle screw with modified pedicle screw augmentation technique using PMMA and performed an L3/4/5 pedicle screw fixation without hook or operation field extension. This modified technique is a kind of transpedicular stiffness augmentation using PMMA for the dead space around the loosed screw. After filling the dead space with 1-2 cc of PMMA, we inserted a small screw. Once the PMMA hardened, we removed the small screw and inserted a thicker screw along the existing screw threading to improve the pedicle screws' pullout strength. At 10 months' follow-up, x-ray showed strong fusion of L3/4/5. The visual analogue scale (VAS) of his back pain was improved from 9 to 5. This modified transpedicular screw augmentation with PMMA using anchoring effect is a simple and effective surgical technique for pedicle screw loosening. However, clinical analyses of long-term follow-up and biomechanical studies are needed.
Instrument failure; Osteoporosis; Pedicle screw loosening; PMMA; Pseudoarthrosis; Surgical technique
A cervical radiculopathy is the most common symptom of cervical degenerative disease and its natural course is generally favorable. With a precise diagnosis using appropriate tools, the majority of patients will respond well to conservative treatment. Cervical radiculopathy with persistent radicular pain after conservative treatment and progressive or profound motor weakness may require surgery. Options for surgical management are extensive. Each technique has strengths and weaknesses, so the choice will depend on the patient's clinical profile and the surgeon's judgment.
Cervical radiculopathy; Diagnosis; Surgery
The purpose of this study is to identify the relationship between asymptomatic urinary tract infection (aUTI) and postoperative spine infection.
A retrospective review was done in 355 women more than 65 years old who had undergone laminectomy and/or discectomy, and spinal fusion, between January 2004 and December 2008. Previously postulated risk factors (i.e., instrumentation, diabetes, prior corticosteroid therapy, previous spinal surgery, and smoking) were investigated. Furthermore, we added aUTI that was not previously considered.
Among 355 patients, 42 met the criteria for aUTI (Bacteriuria ≥ 105 CFU/mL and no associated symptoms). A postoperative spine infection was evident in 15 of 355 patients. Of the previously described risk factors, multi-levels (p < 0.05), instrumentation (p < 0.05) and diabetes (p < 0.05) were proven risk factors, whereas aUTI (p > 0.05) was not statistically significant. However, aUTI with Foley catheterization was statistically significant when Foley catheterization was added as a variable to the all existing risk factors.
aUTI is not rare in elderly women admitted to the hospital for lumbar spine surgery. The results of this study suggest that aUTI with Foley catheterization may be considered a risk factor for postoperative spine infection in elderly women. Therefore, we would consider treating aUTI before operating on elderly women who will need Foley catheterization.
Asymptomatic UTI; Postoperative spine infection; Elderly women
Spontaneous intracranial hypotension is often idiopathic. We report on a patient presenting with symptomatic intracranial hypotension and pain radiating to the right leg caused by a transdural lumbar disc herniation. Magnetic resonance (MR) imaging of the brain revealed classic signs of intracranial hypotension, and an additional spinal MR confirmed a lumbar transdural herniated disc as the cause. The patient was treated with a partial hemilaminectomy and discectomy. We were able to find the source of cerebrospinal fluid leak, and packed it with epidural glue and gelfoam. Postoperatively, the patient's headache and log radiating pain resolved and there was no neurological deficit. Thus, in this case, lumbar disc herniation may have been a cause of spontaneous intracranial hypotension.
Spontaneous intracranial hypotension; Orthostatic headache; Lumbar disc herniation
Malignant peripheral nerve sheath tumors (MPNSTs) are very rare tumors. We experienced a case of MPNST in the cervical paraspinal space which was not associated with neurofibromatosis. The tumor located in left C6-7 foramen and compressed C7 root. The tumor was removed through the occipital triangle. We report a case of the primary cerivcal MPNST in a patient who did not have neurofibromatosis-1.
Malignant peripheral nerve sheath tumor; Cervical paraspinal space; Occipital triangle