Effects of Glycogen Synthase Kinase Inhibitor on Glioblastoma Multiforme Cell Line via Apoptosis and Cell Signaling Pathways.

AIM: To investigate the apoptotic and molecular effects of glycogen synthase kinase-3 (GSK-3) in glioblastoma multiforme (GBM). MATERIAL AND METHODS: Human primary glioblastoma cell line (U-87 MG) and the human fetal glial cell line (SVGp12) were used. The cells were exposed to the different doses of GSK inhibitor for 24, 48 and 72 hours. Induction of apoptosis was assessed by DNA fragmentation (TUNEL) assay. EGFR and NF-kB expression was evaluated by immunofluorescence analyses. RESULTS: GSK-3 inhibitor IX induced cytotoxicity and apoptosis in dose-dependent manner in GBM cells. Our results indicated that GSK-3 inhibitor IX induces apoptosis, resulting in a significant decrease in the expression of NF-kB and EGF. CONCLUSION: Inhibition through GSK-3 has been found promising in creating therapeutic management of GBM cells. Proliferation, differentiation, cell cycle regulation, and apoptosis are mechanisms that must be interpreted as a whole. Components associated with EGFR, NF-kB, and apoptosis affect the mechanism solely and collectively. Our collective data suggest that GSK-3 inhibitor IX inhibited cellular proliferation and induced apoptotic events by modulating EGFR and NF-kB expression in GBM cells. GSK-3 inhibition holds promise for the development of new approaches for the therapeutic management of GBM cells.

Neuroprotective Effects of Oleocanthal, a Compound in Virgin Olive Oil, in a Rat Model of Traumatic Brain Injury.

AIM: To evaluate the neuroprotective effects of deocanthal OC in a rat model of traumatic brain injury (TBI). MATERIAL AND METHODS: Twenty-six adult male, Wistar albino rats were used. The rats were divided into 4 groups. Group 1 was the sham group (n=5). Group 2 was the trauma group (n=5) where rats were treated with 10 mg/kg saline intraperitoneally (IP) twice a day. Groups 3 and 4, rats were treated with 10 (group 3, n=8) or 30 (group 4, n=8) mg/kg OC IP twice a day. For each group, brain samples were collected 72 hours after injury. Brain samples and blood were evaluated with histopathological and biochemical methods. RESULTS: Histopathological evaluation revealed a significant difference between Group 2 and Group 4. Biochemical findings demonstrated that the oxidative stress index was highest in Group 2 and lowest in Group 4. CONCLUSION: OC has a protective effect on neural cells after TBI. This effect is achieved by reducing oxidative stress and apoptosis.

Are Herniated Cerebellar Tonsils the Main Culprit of Chiari Malformation Type I Symptoms? The Brainstem Compression Hypothesis seems to be Re-Elucidated and Revised.

AIM: The Chiari Malformation I (CM I) and the tethered cord syndrome (TCS) are both congenital abnormalities whose mechanisms are still not fully understood. The association of CM I and TCS has been reported only a few times previously. MATERIAL AND METHODS: This retrospective study included 7 patients who were diagnosed with CM I and TCS, managed by cutting of the filum terminale. RESULTS: The mean follow-up period was 21 months and 28 days. Although all patients underwent an untethering surgical procedure by cutting the filum terminale only, all patients reported significant early postsurgical resolution of CM I symptoms and symptoms related to TCS as well. CONCLUSION: Patients with symptomatic CM I, even if lumbar MRI is normal and the patient asymptomatic for TCS, may have tethered spinal cord at the same time. It seems it would be worthwhile to investigate CM I patients for occult TCS with spinal somatosensory evoked potentials.

Effects of lacosamide "a novel antiepileptic drug" in the early stages of chicken embryo development.

INTRODUCTION: Antiepileptic drugs (AEDs) are teratogens and confer a risk of congenital malformation. The estimated prevalence of major congenital malformations such as cardiac defects, facial clefts, hypospadias, and neural tube defects in epileptic women is 4-10 %, which represents a two- to fourfold increase in pregnant women compared to the general population. However, there are no clear data for newer drugs. Lacosamide (LCM), a novel AED, is the first of the third-generation AEDs to be approved as adjunctive therapy for the treatment of partial-onset seizures. There are no data on the pharmacokinetics of LCM during pregnancy, and only some published data have reported on its effects during pregnancy. METHODS: In this study, three different doses of LCM (0.12, 0.5, and 1.60 mg in 0.18 mL) were applied under the embryonic disks of specific pathogen-free Leghorn chicken embryos after a 30-h incubation. Incubation was continued for 80 h, at which time all embryos were evaluated macroscopically and microscopically. RESULTS: There was growth retardation in all of the LCM-treated groups. Major malformations increased in a dose-dependent manner and were mostly observed in the supratherapeutic group. CONCLUSION: Based on our data, LCM may cause growth retardation or major congenital malformations. Nevertheless, more extensive investigations of its reliability are needed.

Scoliosis may be the first symptom of the tethered spinal cord.

BACKGROUND: Tethered cord syndrome (TCS) is a progressive clinical entity that arises from abnormal spinal cord tension. Scoliosis may be a unique symptom in TCS. The aim of this study is to investigate prognosis after releasing the filum terminale in scoliosis due to TCS with/without findings in magnetic resonance imaging (MRI) and to draw attention to the importance of somatosensorial evoked potentials (SSEP) on the differential diagnosis of idiopathic scoliosis versus scoliosis due to TCS with normal appearance of filum terminale and conus medullaris. MATERIALS AND METHODS: Eleven female and seven male patients with progressive scoliosis were included in the study. They were evaluated radiologically, SSEP and urodynamical studies. Preoperative and postoperative anteroposterior full spine X-rays were obtained for measuring the Cobb's angle. MRI was performed in all cases for probable additional spinal abnormalities. All patients underwent filum terminale sectioning through a L5 hemilaminectomy. The resected filum terminale were subjected to histopathological examination. RESULTS: The mean Cobb angle was 31.6° (range 18°-45°). Eight patients (44.45%) had a normal appearance of filum terminale and normal level conus medullaris in MRI, but conduction delay and/or block was seen on SSEP. In the histopathological examination of filum terminale dense collagen fibers, hyaline degeneration and loss of elastic fibers were observed. Postoperatively none of the patients showed worsening of the Cobb angle. Three patients showed improvement of scoliosis. CONCLUSION: In TCS presented with scoliosis, untethering must be performed prior to the corrective spinal surgery. Absence of MRI findings does not definitely exclude TCS. SSEP is an important additional guidance in the diagnosis of TCS. After untethering, a followup period of 6 months is essential to show it untethering helps in stopping the progress of the scoliotic curve. In spite of non progression (curve stopped lesser than 45°) or even improvement of scoliosis, there may be no need for major orthopedic surgical intervention.

Neuroprotective effects of bone marrow-derived mesenchymal stem cellsand conditioned medium in mechanically injured neuroblastoma cells.

BACKGROUND/AIM: Bone marrow-derived mesenchymal stem cells (BMSCs) possess self-renewal characteristics that distinguish them from other cell types. Recent studies have focused on the effects of conditioned medium (CM) that includes the extracellular matrix. Here we examined the neuroprotective effects of BMSCs and CM on damaged neuroblastoma cells. MATERIALS AND METHODS: The cells were divided into five groups: 1) healthy controls, 2) damaged cells alone, 3) damaged cells treated with BMSCs, 4) damaged cells treated with CM, and 5) damaged cells treated with both BMSCs and CM. Neuroprotective effects were then evaluated based upon the levels of oxidative stress, antitransforming growth factor ß1 (anti-TGFß1) production, and apoptosis. RESULTS: Significant differences were observed between healthy controls and damaged cells (P < 0.001), as well as between damaged cells and those treated with BMSCs alone (P < 0.05), CM alone (P < 0.05), and both BMSCs and CM in combination (P < 0.01). Among the treated groups, the strongest neuroprotective effects were seen in cells treated with both BMSCs and CM. CONCLUSION: These results show that both BMSCs and CM exhibit neuroprotective effects in damaged neuroblastoma cells. The strongest benefits were seen following treatment with both BMSCs and CM.

Tethered Cord Syndrome in Adults: Experience of 56 Patients.

AIM: The aim of this study was to describe the results of surgery performed in a group of adult patients with tethered cord syndrome with their outcomes. MATERIAL AND METHODS: This retrospective study included 56 patients. There were 38 females and 18 males. All patients were older than 18 years. RESULTS: The mean age at referral was 36 years and 1 month. The mean follow-up period was 10 months 27 days. 95% of all patients with back and leg pains improved and 5% remained the same. Three patients with motor deficits remained the same in the postoperative period. Of the 16 patients with urological complaints, 10 improved, 5 unchanged and 1 patient died in the postoperative first day due to pulmonary embolism. CONCLUSION: The syndrome of tethered cord may be a situation to be treated even in the elderly in case of normal level conus medullaris and filum terminale with a normal appearance as well as a low-lying conus and thick filum. To prevent overlooking the diagnosis of tethered cord and/or unnecessary spinal surgeries, the tethered cord syndrome should be remembered in the differential diagnosis list in the presence of back and leg pains, neurological deficits or urological complaints.

Cutting filum terminale is very important in split cord malformation cases to achieve total release.

AIM: Split cord malformations (SCMs) are rare congenital anomalies of the vertebrae and the spinal cord. Tethered cord syndrome (TCS) is a clinical condition of various origins that arises from tension on the spinal cord. Radiographic findings may include and/or associate split cord malformations and the other neural tube defects. However, the spinal cord can even be tethered by a filum terminale with normal appearance and normal level conus medullaris in magnetic resonance imaging (MRI). The aim of our study is to show whether SMC patients with normal or abnormal MRI findings had all histological abnormal filum terminale and also to show that the standard SCM repairing operation without cutting filum will not achieve total release. MATERIAL AND METHODS: We have reviewed 33 SCM patients between July 2005 and December 2013. They were operated by adding untethering procedure of filum terminale following standard surgical intervention, and a part of the filum was taken for histopathological examination even though MRI did not show the presence of abnormality of filum terminale. RESULTS: We found that abnormal filum terminale with a normal appearance may had dense collagen fibers, wide and numerous capillaries, and hyaline formation, while normal filum terminale is a mixture of collagen fibers and blood vessels. We did not obtain positive Verhoeff elastic fiber staining. The elastic fibers had disappeared in all fila terminalia, except control cadaver group. CONCLUSION: Our results showed that all fila of SCM patients had loss of elastic fibers and increased of hyalinization, which means loss of elasticity of filum terminale. Less severe traction may remain asymptomatic in childhood and present with neurological dysfunction later in life. For this reason, surgical procedure of SCM patients including releasing of filum terminale seems more beneficial for the patients and be better for long term.

Congenital dermal sinus tract of the spine: experience of 16 patients.

Congenital dermal sinus tract is a rare entity which lined by epithelial cells and can end anywhere between subcutaneous planes to thecal sac. These tracts may be accompanied with other pathologies such as lipomyelomeningocele, myelomeningocele, split cord malformation, tethered cord, filum abnormality and inclusion tumors and treatment includes resection of tract with intradural exploration. The authors review their experience with 16 cases. Clinical, radiological appearance and treatment of these lesions discussed with literature review.

TGF-ßs and Smads activities at the site of failed neural tube in the human embryos.

AIM: Transforming growth factor ß (TGF-ß) and Smads control intracellular signaling pathways in neurulation. Although previously reported similar experimental animal studies, the aim of this human study is to investigate the expression of TGF-ß (1,2,3) and Smads (1,2,3,6,7) in aborted human fetuses with myeloschisis. MATERIAL AND METHODS: Twelve human fetuses with neural tube defect were obtained. They were stained with antibodies against TGF-ß1, TGF-ß2, TGF-ß3, Smad (1,2,3), Smad 6 and Smad 7 using the indirect immunohistochemical technique. RESULTS: We noted mild immune reactivity of TGF-ß1 and TGF-ß2 in the open neural plate, motor neurons and surrounding tissue. Strong immune reactivity of TGF-ß3 was shown in only open neural plate and surrounding tissue. Immunoreactivity of all Smads noted negative except Smad7. CONCLUSION: These results suggested at the site where the neural tube failed to close, TGF-ß 1,2 and Smads 1,2,3,6 do not continue their activity and decrease with internal timing of embryonic development. Additionally ectodermal layers are considered by embryo as "not closed wound" and TGF-ß3 activity may be an effort to repair the failed closure.

Evaluation of the effects of mobile phones on the neural tube development of chick embryos.

AIM: The objective of this study is to examine the effects of radiation of mobile phones on developing neural tissue of chick embryos. MATERIAL AND METHODS: There were 4 study groups. All Groups were placed in equal distance, from the mobile phones. Serial sections were taken from each Group to study the neural tube segments. RESULTS: The TUNEL results were statistically significant (p < 0.001) at 30 and 48 hours in the third Group. We found low Bcl-2 levels partly in Group 4 and increased activity in Group 3. Caspase-3 was negative in the 48 and 72 hours in the Control Group, had moderate activity in the third Group 3, weak activity in the 48 hour, and was negative in the 72 hour in other groups. Caspase-9 immunoreactivity was weak in Group 1, 2 and 3 at 30 hours and was negative in Group 1 and 4 at 48 and 72 hours. Caspase-9 activity in the third Group was weak in all three stages. CONCLUSION: Electromagnetic radiation emitted by mobile phones caused developmental delay in chick embryos in early period. This finding suggests that the use of mobile phones by pregnant women may pose risks.

A new guide tube for odontoid screw fixation for unstable odontoid fractures: report of 6 case series.

AIM: We describe a modified form of traditional open surgery with a new guide tube. This guide tube permits anterior screwing of odontoid in a shorter time with a more simple technique as compared to traditional open surgery, endoscopic and percutaneous surgeries. MATERIAL AND METHODS: Our series includes 6 patients who were operated for unstable odontoid fracture. We used a new guide tube for anterior odontoid screw fixation. This guide tube was designed by the first author to facilitate the insertion of the K-wire for placement of a cannulated lag screw. RESULTS: Successful placement of the odontoid screws and immediate spinal stabilization were achieved in all patients. Solid fusion was observed during follow-up time in all patients. CONCLUSION: This screw insertion technique for odontoid screw fixation provides a minimally invasive, safe and easy surgery in contrast to other surgical approaches.

Preoperative and postoperative evaluation of somatosensorial evoked potentials of upper extremities in cervical intervertebral disc herniation.

This study aims to determine the dysfunction caused by existing pathological condition in structures involved in the transfer of sensory functions of the neural system in cervical disc herniation, and to establish whether or not the level and degree of this anatomical damage can be anticipated by SEP (Somatosensorial Evoked Potentials). We compared the obtained SEP values for statistical significance using the Friedman Variation Analysis. In parameters with statistical significance, the Wilcoxon Signed Rank test was used to identify when significant improvements occurred. The study found that the statistical data of the latency of the N14 wave originating from the dorsal column nuclei of the medulla spinalis and dorsal column gray matter improved (p < 0.05) in the postoperative period compared with the preoperative values. Using the Wilcoxon Signed Rank test, we studied postoperative months separately in regard to the difference in the latency of the N14 wave, and found the statistically significant improvement to be marked particularly in months 3 and 6 postoperatively (p < 0.05). In conclusion, we suggest that SEP is a useful tool to check the functional condition of the dorsal spinal column. The benefit of the SEP utilization is the ability to determine the severity of the pathological condition preoperatively and follow the patient's functional postoperative improvement.

Missing screw as a rare complication of anterior cervical instrumentation.

Although anterior cervical arthrodesis is an effective procedure for the treatment of cervical disorders, the method has some complications. Here, we describe this rare complication of cervical instrumentation with a literature review. A 23-year-old male patient was operated for a C6-C7 dislocation. At postoperative month 10, he presented with hemoptysis and dysphagia. Cervical roentgenograms showed anterior migrations of one broken screw and a plate-locking screw at the C6 corpus. One screw was missing. We concluded that the missing screw had perforated the esophagus and had been eliminated spontaneously through the gastrointestinal tract. No screw should migrate. Even loose screws should be noted in follow-up X-ray studies. If such findings are detected, a second operation for revision should be considered as soon as possible to prevent potentially fatal complications.

Differences in individual susceptibility affect the development of trigeminal neuralgia.

Trigeminal neuralgia is a syndrome due to dysfunctional hyperactivity of the trigeminal nerve, and is characterized by a sudden, usually unilateral, recurrent lancinating pain arising from one or more divisions of the nerve. The most accepted pathogenetic mechanism for trigeminal neuralgia is compression of the nerve at its dorsal root entry zone or in its distal course. In this paper, we report four cases with trigeminal neuralgia due to an unknown mechanism after an intracranial intervention. The onset of trigeminal neuralgia after surgical interventions that are unrelated to the trigeminal nerve suggests that in patients with greater individual susceptibility, nerve contact with the vascular structure due to postoperative pressure and changes in cerebrospinal fluid flow may cause the onset of pain.

[Cerebral cystic echinococcosis in the light of our experience]. / Klinik deneyimlerimiz isiginda serebral kistik ekinokokkoz.

Cerebral cystic echinococcosis (CCE) is rare and constitutes 1-2% of all cystic echinococcosis. The cysts are usually solitary and most frequently located in the supratentorial region. CCE is classified as primary and secondary. The primary cysts developed from the embryos which escaped from the filter systems are more frequent and usually solitary and fertile. The secondary cysts result from spontaneous, traumatic or surgical rupture of the primary CCE by embolization of scolices. They are usually multiple and infertile and do not have brood capsule or scolices. Symptoms usually develop slowly and are usually due to increased intracranial pressure and depend on the location of the cyst. Diagnosis is made by evaluation of both clinical and laboratory findings. Computed tomography and magnetic resonance imaging is successful in the diagnosis. The cysts are observed as spherical, well defined, with thin regular margins by these methods. The most appropriate treatment method is total surgical removal of the cyst without rupture by using Dowling's method. However, when it is not possible to remove without rupture, the cyst should be removed totally after puncture and aspiration of contents of the cyst. After removal of large cysts, complications such as porencephalic cysts and subdural hemorrhage can occur postoperatively.

Intracranial hydatid cyst is a rare cause of midbrain herniation: A case report and literature review.

Hydatid disease is a parasitic infection affecting the brain in about 2% of the cases. Brain involvement is most commonly observed in children. Here, we report a 13-year-old male patient who presented with headache, nausea, and vomiting. Before cranial computed tomography (CT) was performed, the patient had generalized epileptic seizures. He was disoriented, and had anisocoria with dilatation of the right pupilla. CT showed a cystic lesion of 10-cm diameter in the right temporoparietal region that had caused a shift of the midline structures to the contralateral side; an urgent operation was performed as there were signs of midbrain herniation.

Urinary incontinence triggered by stretching exercises.

A 47-year-old female patient who experienced urinary urgency after having stretching exercises of her legs is presented. Stretching of the legs are thought to be responsible for conus medullaris tethering which in turn causes urinary complaints. What is interesting in this case is that her complaints about urinary urgency stopped as she quit stretching exercise movements of her legs. There are some examples of such cases in the literature. The urinary urgency after stretching exercises warned us to investigate this patient in regard to tethered conus medullaris. Tethering of the conus medullaris can be temporary and can cause reversible functional disorders of the bladder. Incontinence at any age should be evaluated cautiously as it could be a sign of an underlying important developmental failure.