Cortical bone trajectory fixation cause low compression force in anterior vertebral column.

Background: The cortical bone trajectory (CBT) screws follow a caudocephalad and lateral path from the pedicle to the vertebral body. The bone fusion rate of CBT fixation is equal to or lower than conventional pedicle screw fixation. It remains unclear whether or not CVT screws exert equally compressive forces across the vertebral column. In this study, we intraoperatively examined the insertional torque of CBT screws, and investigated the compression loading and pressure distribution in conventional and CBT fixation using pig bones. Methods: The insertional torque was measured for a total of 115 CBT screws. Detailed positions of these screws were retrospectively confirmed using CT scans. Screw loosening and interbody fusion were examined 1 year after surgery. In the experiment using pig bones, we inserted screws by conventional trajectory (n = 3) and CBT (n = 4). Results: Multiple regression analysis showed that the total screw length, the distance from the screw to the medial border of the pedicle and the distance from the superior endplate of the vertebrae were significant independent factors affecting the insertional torque. There was no significant association between the insertional torque and the radiographic bone fusion rate 12 months after surgery. The average pressure and the compression loading in the anterior column were significantly lower in CBT group. Conclusion: These results suggested that the long CBT screws as close to the endplate had high insertional torque, but the anterior column in CBT fixation showed low compression force leading to the insufficient holding intervertebral cage. CBT screws may cause the micromotion of cages, which lowers the bone fusion rate.

An increase in the posterior subarachnoid space accelerates the timing of syrinx resolution after foramen magnum decompression of type I Chiari malformation.

Syrinx resolution has been associated with an increase in the size of the posterior subarachnoid space (pSAS) after foramen magnum decompression (FMD) for type I Chiari malformation (CM1). The present study investigated the influence of pSAS increase on syrinx resolution and symptom improvement after FMD. 32 patients with CM1 with syrinx were analyzed retrospectively. FMD was performed for the 24 patients with CM1 with syrinx. pSAS areas were measured on sagittal magnetic resonance images. Neurological symptoms were grouped into three clinical categories and scored. The rates of symptom improvement in the CM1 patients with syrinx after FMD was 19.7% ± 12.9%. The mean times to the improvement of neurological symptoms in CM1 patients with syrinx after FMD was 23.4 ± 50.2 months. There were no significant differences between the patients with and without improvement of syrinx after FMD with regard to the age, length of tonsillar herniation, BMI, and preoperative pSAS areas. The rate of increase in the pSAS areas was significantly higher in the group with syrinx improvement within 1 year (p < 0.0001). All patients with a > 50% rate of increase in the pSAS area showed syrinx improvement. Our results suggested that the increasing postoperative pSAS area accelerated the timing of syrinx resolution.

Report of a familial case of proatlas segmentation abnormality with late clinical onset.

Although proatlas segmentation abnormalities as developmental remnants around the foramen magnum have been reported in postmortem studies, they are rarely documented in a clinical setting. This report details the clinical and radiological characteristics of a rare case of proatlas segmentation abnormalities with clinical onset during the seventh decade of life. This case was suspected to have a familial factor. We also review the literature regarding this condition.

Promotion of astrocytoma cell invasion by micro RNA-22 targeting of tissue inhibitor of matrix metalloproteinase-2.

OBJECTIVE Diffuse astrocytomas (DAs) have a high recurrence rate due to diffuse infiltration into the brain and spinal cord. Micro RNAs (miRNAs) are small noncoding RNAs that regulate gene expression by binding to complementary sequences of target messenger RNA (mRNA). It has been reported that miRNA-22 (miR-22) is involved in the invasion of some cancer cell lines. The aim of this study was to identify the biological effects of miR-22 in regard to the invasion of human DAs. METHODS The authors evaluated whether the level of miR-22 is elevated in human spinal DAs by using miRNA chips. Next, the role of miR-22 in 1321N1 human astrocytoma cells was investigated. Finally, to elucidate whether miR-22 promotes invasion by astrocytoma cells in vivo, the authors transplanted miR-22 overexpressed astrocytoma cells into mouse thoracic spinal cord. RESULTS The miR-22 significantly upregulated the invasion capacity of 1321N1 cells. Computational in silico analysis predicted that tissue inhibitor of matrix metalloproteinase-2 (TIMP2) is a target gene of miR-22. This was confirmed by quantitative reverse transcription polymerase chain reaction and Western blotting, which showed that miR-22 inhibited TIMP2 mRNA and protein expression, respectively. Luciferase reporter assays demonstrated that miR-22 directly bound the 3'-untranslated regions of TIMP2. The authors further showed that miR-22 promoted invasiveness in 1321N1 astrocytoma cells when transplanted into mouse spinal cord. CONCLUSIONS These data suggest that miR-22 acts to regulate invasion of 1321N1 astrocytoma cells by targeting TIMP2 expression. Additional studies with more cases and cell lines are required to elucidate the findings of this study for a novel treatment target for spinal DAs.

Significance of the Pars Interarticularis in the Cortical Bone Trajectory Screw Technique: An In Vivo Insertional Torque Study.

STUDY DESIGN: Retrospective study. PURPOSE: Cortical bone trajectory (CBT), a more medial-to-lateral and shorter path than the traditional one for spinal fusion, is thought to be effective for severely degenerated vertebrae because screws are primarily stabilized at the posterior elements. We evaluated the efficacy of this approach through in vivo insertional torque measurement. OVERVIEW OF LITERATURE: There has been only one prior in vivo study on CBT insertional torque. METHODS: Between January 2013 and April 2014, a total of 22 patients underwent posterior lumbar fusion using the CBT technique. The maximum insertional torque, which covers the radial strength needed for insertion, was measured for 113 screws, 8 of which were inserted for L5 spondylolysis. The insertional torque for cases with (n=8) and without (n=31) spondylolysis of L5 were compared using one-way analysis of variance (ANOVA). To evaluate vertebral degeneration, we classified 53 vertebrae without spondylolysis by lumbar radiography using semiquantitative methods; the insertional torque for the 105 screws used was compared on the basis of this classification. Additionally, differences in insertional torque among cases grouped by age, sex, and lumbar level were evaluated for these 105 screws using ANOVA and the Tukey test. RESULTS: The mean insertional torque was significantly lower for patients with spondylolysis than for those without spondylolysis (4.25 vs. 8.24 in-lb). There were no statistical differences in insertional torque according to vertebral grading or level. The only significant difference in insertional torque between age and sex groups was in men <75 years and women ≥75 years (10 vs. 5.5 in-lb). CONCLUSIONS: Although CBT should be used with great caution in patient with lysis who are ≥75 years, it is well suited for dealing with severely degenerated vertebrae because the pars interarticularis plays a very important role in the implementation of this technique.

A Pilot Clinical Study of Olfactory Mucosa Autograft for Chronic Complete Spinal Cord Injury.

Recent studies of spinal cord axon regeneration have reported good long-term results using various types of tissue scaffolds. Olfactory tissue allows autologous transplantation and can easily be obtained by a simple biopsy that is performed through the external nares. We performed a clinical pilot study of olfactory mucosa autograft (OMA) for chronic complete spinal cord injury in eight patients according to the procedure outlined by Lima et al. Our results showed no serious adverse events and improvement in both the American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade and ASIA motor score in five patients. The preoperative post-rehabilitation ASIA motor score improved from 50 in all cases to 52 in case 2, 60 in case 4, 52 in case 6, 55 in case 7, and 58 in case 8 at 96 weeks after OMA. The AIS improved from A to C in four cases and from B to C in one case. Motor evoked potentials (MEPs) were also seen in one patient, reflecting conductivity in the central nervous system, including the corticospinal tract. The MEPs induced with transcranial magnetic stimulation allow objective assessment of the integrity of the motor circuitry comprising both the corticospinal tract and the peripheral motor nerves.We show the feasibility of OMA for chronic complete spinal cord injury.

Radiological Evaluation of the Initial Fixation between Cortical Bone Trajectory and Conventional Pedicle Screw Technique for Lumbar Degenerative Spondylolisthesis.

STUDY DESIGN: Retrospective study. PURPOSE: To compare initial fixation using the cortical bone trajectory (CBT) technique versus conventional pedicle screws (PS) in radiographs of postsurgical lumbar degenerative spondylolisthesis. OVERVIEW OF LITERATURE: Few reports have documented the holding strength of CBT technique for spondylolisthesis cases. METHODS: From October 2009 to June 2014, 21 cases of degenerative spondylolisthesis were surgically treated in our institution. Ten were treated with conventional PS technique and 11 of with CBT technique. Mean lumbar lordosis and percent slippage were evaluated preoperatively, immediately after surgery, and 6 months and 1 year postoperatively using radiographs. We also investigated percent loss of slip reduction. RESULTS: There were statistically significant differences between preoperative percent slippage and postoperative slippage in both PS and CBT procedures over 1 year, and both techniques showed good slip reduction. On the other hand, lumbar lordosis did not change significantly in either the PS or CBT groups over 1 year. CONCLUSIONS: CBT technique showed similarly good initial fixation compared with the PS procedure in the treatment of lumbar degenerative spondylolisthesis.

Motor evoked potential and voluntary EMG activity after olfactory mucosal autograft transplantation in a case of chronic, complete spinal cord injury: case report.

The efficacy of olfactory mucosal autografts (OMAs) for chronic spinal cord injury (SCI) has been reported, but there is no report documenting electrophysiological conductivity via the emergence of motor evoked potentials (MEPs). We report the case of a 39-year-old man with chronic, complete SCI at T8, who exhibited MEPs after OMA transplantation, and, with intensive rehabilitation, was ultimately able to ambulate with short leg braces and Lofstrand crutches. The initial injury occurred in a motor vehicle accident in November 1999 and resulted in a complete loss of sensorimotor function below T8. OMA transplantation to the injury site was performed in March 2010 in combination with intensive pre- and postoperative rehabilitation. The patient exhibited voluntary electromyograph (EMG) activity and MEPs at 96 and 144 weeks after transplantation and he was was ambulatory with short leg braces and Lofstrand crutches at 144 weeks after transplantation. We were able to elicit MEPs after OMA with intensive rehabilitation. To our knowledge, this is the first report of recovery of electrophysiological conductivity in the spinal cord after any type of treatment for chronic, complete SCI.

"Do Not Follow the Tail": A Practical Approach to Remove a Sheared Lumbar Catheter Fragment Avoiding Its Migration into the Spinal Canal.

BACKGROUND: Catheter shearing is one of the most common complications of various neurosurgical modalities that use an intrathecal lumbar catheter. The sheared catheter fragment often can spontaneously migrate into the spinal canal; however, in some cases, the end of the fragment will remain outside the spinal canal. In this situation, the consulting neurosurgeons may try to retrieve the catheter fragment by approaching it directly through the catheter tract. This simple maneuver, however, can cause the fragment to slip into the spinal canal before it is secured, as we experienced recently in 2 cases. Because the fragment of the sheared catheter slipped while manipulating it within the catheter tract, we suggest that surgeons not approach the fragment along the tract to prevent it from migrating downward. METHODS: Using the operative findings of an illustrative case, we describe how to avoid downward migration of the catheter fragment when retrieving a sheared lumbar catheter. RESULTS: We found that the sheared catheter of a lumbar-peritoneal shunt was slowly slipping along with the pulsatile movement of cerebrospinal fluid within the catheter tract. We successfully retrieved the fragment by approaching it from outside the catheter tract. CONCLUSIONS: We propose that surgeons approach the fragment from outside of the catheter tract. One should keep in mind a simple phrase, 'Do not follow the tail', when retrieving the sheared lumbar catheter fragment.

Extramedullary Conus Ependymoma Involving a Lumbar Nerve Root with Filum Terminale Attachment.

PURPOSE: In the current report, we describe a case of an extramedullary ependymoma involving a lumbar nerve root near conus medullaris. Spinal ependymomas commonly present as intramedullary tumors in the cervical or thoracic cord or as tumors arising from the conus medullaris or the filum terminale. In this case, we showed an extramedullary conus ependymoma involving a lumbar nerve root with filum terminale attachment. CASE PRESENTATION: A 69-year-old woman presented with lower back pain, but without sensory disturbance or motor weakness in her lower extremities. CLINICAL ASSESSMENT: Magnetic resonance imaging revealed an intradural mass at T12-L1 at the conus medullaris, which was totally resected. Histopathology revealed a non-myxopapillary ependymoma (WHO grade 2). Postoperatively, the patient did well and displayed no neurological deficits. Moreover, no radiotherapy was required. CONCLUSIONS: This report documented a rare case of intradural extramedullary ependymoma located at the conus medullaris, involving the lumbar nerve root, and attached to the filum terminale. Although extramedullary ependymomas at this region are more frequently classified as myxopapillary, histopathological examination revealed this tumor as a non-myxopapillary ependymoma.

Clear Zone Formation around Screws in the Early Postoperative Stages after Posterior Lumbar Fusion Using the Cortical Bone Trajectory Technique.

STUDY DESIGN: Retrospective study. PURPOSE: To evaluate the initial fixation using the cortical bone trajectory (CBT) technique for posterior lumbar fusion through assessment of the clear zones around the screws and the risk factors involved. OVERVIEW OF LITERATURE: Postoperative radiolucent zones (clear zones) are an indicator of poor conventional pedicle screw fixation. METHODS: Between January 2013 and April 2014, 19 patients (8 men and 11 women) underwent posterior lumbar interbody fusion or posterior lumbar fusion using the CBT technique. A total of 109 screws were used for evaluation with measurement of the maximum insertional torque of last two screw rotations. Clear zone-positivity on plain radiographs was investigated 6 months after surgery. The relation between intraoperative insertional torque and clear zone-positivity was investigated by one-way analysis of variance. In addition, the correlation between clear zone-positivity and gender, age (<75 years old or >75 years old), or operative stabilization level (<2 or >3 vertebral levels) was evaluated using the chi-square test. RESULTS: Clear zones were observed around six screws (5.50%) in five patients (26.3%). The mean insertional torque (4.00±2.09 inlbs) of clear zone-positive screws was lower than that of clear zone-negative screws (8.12±0.50 in-lbs), but the difference was not significant. There was a significant correlation between clear zone-positivity and operative level of stabilization. CONCLUSIONS: The low incidence of clear zone-positive screws indicates good initial fixation using the CBT technique. Multilevel fusions may be risk factors for clear zone generation.

Isthmus-guided Cortical Bone Trajectory Reduces Postoperative Increases in Serum Creatinine Phosphokinase Concentrations.

OBJECTIVE: This study aimed to determine whether an isthmus-guided cortical bone trajectory (CBT) technique provides better clinical outcomes than the original cortical bone trajectory CBT technique for screw fixation. METHODS: A consecutive series of 21 patients with lumbar spondylolisthesis who had undergone CBT screw fixation using the original technique from June 2012 to February 2013 and 33 who had undergone the isthmus-guided technique from March 2013 to August 2014 was retrospectively reviewed. The number of screws inserted, interbody fusion and screw misplacements, amount of blood loss, and creatinine phosphokinase (CPK) ratios (postoperative day 1 CPK/preoperative CPK) were reviewed to evaluate clinical outcomes and compared between the original and isthmus-guided CBT techniques. RESULTS: Postoperative serum CPK concentrations were significantly lower with the isthmus-guided than the original CBT technique (P < 0.05). There were no significant differences in age, blood loss, or number of screws, vertebral interbody fusions and patients with history of previous decompression surgery at the same level. There was a trend to higher incidence of screw misplacement with the original than the isthmus-guided CBT technique; this difference was not significant (P = 0.53). There were no major intraoperative complications. In all the CBT procedures performed in our institution, almost half (47%) the screw misplacements have occurred at the level of L5 , and most on the right side. CONCLUSIONS: Right-handed operators should take care inserting screws on the right side. From the viewpoint of screw misplacement, isthmus-guided CBT provides superior or equivalent safety to the original CBT technique.

Cervical osteomyelitis with thoracic myelitis and meningitis in a diabetic patient.

A 45-year-old man with a history of untreated diabetes mellitus had a persisting fever, back pain, and diarrhea. The primary care physician diagnosed the patient with the flu and gastroenteritis. The patient developed paraplegia for two weeks and was admitted to another hospital. The physician in this hospital suspected infectious meningitis and myelitis, and administered piperacillin and steroids without cerebrospinal fluid (CSF) examination. On referral to our hospital, he presented a high fever and complete paraplegia. The lumbar puncture revealed a yellowish CSF, polynucleosis, and hypoglycorrhachia. Bacteria were not detected on Gram's staining and were not confirmed by CSF culture. Magnetic resonance imaging (MRI) showed no thoracolumbar lesion and suggested a cervical epidural abscess without any spinal cord compression. He was diagnosed as having osteomyelitis with meningitis and thoracic myelitis. The infection subsided with broad-spectrum antibiotics. After two weeks, bilateral sensorimotor disturbances of the upper extremities appeared. MRI findings showed the epidural abscess compressing the cervical spinal cord. We performed debridement of the epidural abscess. The infection was clinically controlled by using another antibiotic. One month after the infection subsided, a 360° reconstruction was performed. In this case, the misdiagnosis and the absence of CSF examination and culture to detect the pathogenic bacteria at an earlier stage in the patient's disease course might have led to the exacerbation of the pathology.

Isolation of human adult olfactory sphere cells as a cell source of neural progenitors.

Olfactory stem cells are generated from olfactory mucosa. Various culture conditions generate olfactory stem cells that differ according to species and developmental stage and have different progenitor or stem cell characteristics. Olfactory spheres (OSs) are clusters of progenitor or stem cells generated from olfactory mucosa in suspension culture. In this study, adult human OSs were generated and their characteristics analyzed. Human OSs were adequately produced from olfactory mucosa with area over 40 mm(2). Immunocytochemistry (ICC) and fluorescence-activated cell sorting showed that human OSs were AN2 and A2B5-positive. Immunofluorescence analysis of cell type-specific ICC indicated that the number of Tuj1-positive OS cells was significantly elevated. Tuj1-positive cells displayed typical neuronal soma and dendritic morphology. Human OS cells were also immunopositive for MAP2. By contrast, few RIP-, O4-, and GFAP-positive cells were present. These RIP, O4, and GFAP-positive cells did not resemble bona fide oligodendrocytes and astrocytes morphologically. In culture to induce differentiation of oligodendrocytes, human OS cells also expressed neuronal markers, but neither oligodendrocyte or astrocyte markers. These findings suggest that human OS cells autonomously differentiate into neurons in our culture condition and have potential to be used as a cell source of neural progenitors for their own regenerative grafts, avoiding the need for immunosuppression and ethical controversies.

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.

Differences between Cervical Schwannomas of the Anterior and Posterior Nerve Roots in Relation to the Incidence of Postoperative Radicular Dysfunction.

STUDY DESIGN: A retrospective study. PURPOSE: To assess the case files of patients who underwent surgery for cervical dumbbell schwannoma for determining the differences between schwannomas of the anterior and posterior nerve roots with respect to the incidence of postoperative radicular dysfunction. OVERVIEW OF LITERATURE: The spinal roots giving origin to schwannoma are frequently nonfunctional, but there is a risk of postoperative neurological deficit once these roots are resected during surgery. METHODS: Fifteen patients with cervical dumbbell schwannomas were treated surgically. Ten men and 5 women, who were 35-79 years old (mean age, 61.5 years), presented with neck pain (n=6), radiculopathy (n=10), and myelopathy (n=11). RESULTS: Fourteen patients underwent gross total resection and exhibited no recurrence. Follow-ups were performed for a period of 6-66 months (mean, 28 months). Preoperative symptoms resolved in 11 patients (73.3%) but they persisted partially in 4 patients (26.7%). Six patients had tumors of anterior nerve root origin, and 9 patients had tumors of posterior nerve root origin. Two patients who underwent total resection of anterior nerve root tumors (33.3%) displayed minor postoperative motor weakness. One patient who underwent total resection of a posterior nerve root tumor (11.1%) showed postoperative numbness. CONCLUSIONS: Appropriate tumor removal improved the neurological symptoms. In this study, the incidence of radicular dysfunction was higher in patients who underwent resection of anterior nerve root tumors than in patients who underwent resection of posterior nerve root tumors.

A symptomatic spinal extradural arachnoid cyst with lumbar disc herniation.

Spinal epidural arachnoid cyst (EAC) is a rare, usually asymptomatic condition of unknown origin, which typically involves the lower thoracic spine. We report a case of posttraumatic symptomatic EAC with lumbar disc herniation. A 22-year-old man experienced back pain and sciatica after a traffic accident. Neurological examination revealed a right L5 radiculopathy. Magnetic resonance imaging demonstrated a cystic lesion at the L3 to L5 level and an L4-5 disc herniation; computed tomography myelography showed that the right L5 root was sandwiched between the cyst and the herniation. A dural defect was identified during surgery. The cyst was excised completely and the defect was repaired. A herniation was excised beside the dural sac. Histology showed that the cyst wall consisted of collagen and meningothelial cells. Postoperatively the symptoms resolved. Lumbar spinal EACs are rare; such cysts may arise from a congenital dural crack and grow gradually. The 6 cases of symptomatic lumbar EAC reported in the literature were not associated with disc herniation or trauma. In this case, the comorbid disc herniation was involved in symptom progression. Although many EACs are asymptomatic, comorbid spinal disorders such as disc herniation or trauma can result in symptom progression.

A Case of Apoplexy of Rathke's Cleft Cyst Followed by Cerebral Infarction.

Rathke's cleft cyst (RCC) apoplexy is a rare clinical entity. We report a case of apoplexy of an RCC followed by cerebral infarction. A 67-year-old woman was found lying on the street unconscious. She had fallen from her motorbike. On referral to our hospital she gradually regained consciousness and presented with no neurological deficits. CT showed a round and slightly hyperdense area in the suprasellar region. However, the attending physician did not find this abnormal finding on CT and the patient was discharged the same day. Thirteen days after the first emergency visit she developed left hemiparesis and dysarthria. CT showed a round hypodense area in the suprasellar region. The change of the density in the suprasellar region on CT suggested the pituitary apoplexy. CT also showed a low density area in the territory of the right middle cerebral artery, which indicated the cerebral infarction. MR angiography revealed poor visibility and stenotic changes of right middle cerebral arteries. Transsphenoidal surgery was performed. Histopathological findings confirmed a hemorrhagic RCC. Postoperative MR angiography showed that the visibility and stenosis of right middle cerebral arteries were recovered. This is the rare case of apoplexy of an RCC followed by cerebral infarction.

Olfactory sphere cells are a cell source for γ-aminobutyric acid-producing neurons.

Olfactory sphere cells (OSCs) are stem cells generated by culturing olfactory mucosa. Adult rat OSCs express oligodendrocyte progenitor cell (OPC) markers and differentiate into mature oligodendrocytes. Although OSCs also express nestin, a marker of neural stem cells (NSCs), it remains unclear whether adult rat OSCs are multipotent and capable of giving rise to neurons as well as oligodendrocytes. Valproic acid (VPA) is a histone deacetylase inhibitor that has the contradictory capacity to induce both differentiation of NSCs and dedifferentiation of OPCs. This study investigates a potential role for VPA in inducing either differentiation or dedifferentiation of adult rat OSCs. Treatment of OSCs with VPA induced hyperacetylation of histones and decreased cell proliferation in the absence of changes in the number of nestin-positive cells. Furthermore, VPA promoted the genesis of γ-aminobutyric acid (GABA)-producing neurons identified by expression of Tuj1/GAD67/GABA while repressing oligodendrocyte production. These findings suggest that OSCs treated with VPA did not exhibit stem cell properties indicative of dedifferentiation but rather switched to a neuronal identity during their terminal differentiation. OSCs were then transplanted into the hippocampus of rats with kainic acid-induced temporal lobe epilepsy and were systemically given VPA. Although grafted OSCs expressed Tuj1 and GAD67, these cells did not sufficiently inhibit epileptic activity. These results suggest that OSCs are a transplantable cell source for GABA-producing neurons that can be modulated by VPA. However, further investigation is required to develop them for clinical applications.