Mevlut Ozgur Taskapilioglu

Investigation of the dose-dependency of citicoline effects on nerve regeneration and functional recovery in a rat model of sciatic nerve injury.

AIM The aim of this study was to investigate the dose dependence of citicolines previously-reported effects on recovery of peripheral nerve injury. MATERIAL AND METHODS Right sciatic nerves of sixty adult female Wistar Albino rats were incised and primary anastomosis was performed. Rats were then divided into four groups: Control group received 2 ml of saline intraperitoneally, while rats in C-300, C-600 and C-900 groups received 300 μmol/kg, 600 μmol/kg and 900 μmol/kg citicoline dissolved in 2 ml saline, respectively. Rats were tested for sciatic functional index (SFI) on the 4th, 8th and 12th weeks and electrophysiological recordings were obtained on the 12th week. Rats were then sacrificed to investigate nerve adhesions and perform histomorphological examinations. RESULTS Our results showed that rats in C-600 and C-900 groups had significantly lesser neural adhesion and greater SFI and electrophysiological score than those in the Control and C-300 groups (p < 0.05). Mean density and total number of functionally myelinated axons were significantly increased in C-900 group, while perineural scar tissue formation was reduced in all citicoline-treated groups. CONCLUSION We conclude that citicoline exhibits dose-dependent effects on axonal regeneration and recovery without scar formation in a rat model of peripheral nerve incision and primary anastomosis.

Multiple extracranial metastases from secondary glioblastoma: a case report and review of the literature.

Glioblastoma represents extreme anaplasia in astrocytic tumors. In spite of this aggressiveness, extracranial metastasis of glioblastoma is very rare and has been documented in only a few patients in the literature. In this article, a 30-year-old woman with secondary glioblastoma associated with extracranial distant metastasis was presented. In September 2008, an intracranial lesion in the left frontal region was diagnosed by magnetic resonance imaging (MRI) after admission to the hospital by headache and seizure and subsequently resected. The histology of the lesion revealed an anaplastic astrocytoma (grade III). Upon recurrence of the tumor 7 months later, the patient underwent a second craniotomy for recurrence tumor resection. The histological diagnosis was glioblastoma. After radiotherapy and chemotherapy, cranial computerized tomography (CT) and whole body scintigraphy revealed metastatic lesions in the right cervical lymph nodes and the left ischium. A neck dissection and parathyroidectomy on the right side was performed. The cytomorphological and histological features of the tumor supported the diagnosis of metastatic glioblastoma.

CT-Guided High-Level Percutaneous Cervical Cordotomy for Intractable Cancer Pain.

AIM To evaluate the safety and effectiveness of computed tomography-guided high-level percutaneous selective cervical cordotomy (CT-guided HPSCC). MATERIAL AND METHODS CT-guided percutaneous procedures were performed in fifty-nine patients between the years 2004- 2013 for cancer pain. Forty-eight patients with cancer-related body pain were treated with CT-guided HPSCC was evaluated retrospectively. RESULTS CT-guided HPSCC was performed in 33 male and 15 female patients. The mean age was 49.93 years. The distance between skin-dura, anteroposterior diameter and mediolateral diameter was measured as 40 to 71.1 mm, 8 to 88 mm and 8 to 99 mm respectively. The mean postoperative Karnofsky Performance Score (KPS) was 95. Mean preoperative Visual Analog Scale (VAS) score was 9.6, and 3.6 on postoperative day 1. The 6 < sup > th < /sup > month follow-up VAS score was 6.8. Preoperative total sleeping hours in a 24-hour period were 5.5 hours, which increased in the immediate postoperative period to 8.5 hours. The most common pathology treated was bronchogenic carcinoma. Six of the procedures were bilateral and there were no permanent complication due to the procedure. CONCLUSION CT-guided HPSCC is still very effective, cheap and repetitive procedure for cancer pain. The procedure should be performed by experienced surgeons and although there is a hegemony of opioids, the number of surgeons that perform the procedure must be increased.

Effect of Pre/Postconditioning at Temporary Clipping.

Intracranial aneurysms and their treatment is one of the leading problems of neurosurgery that create high mortality and morbidity. The technique of safe clipping is as generally used depends on the temporary occlusion of the cerebral vasculature during surgery. However, there is no exact data about temporary clipping or timing of this procedure. Preconditioning by exposure to sublethal hypoxic stress, hours or days before severe hypoxia, decreases cell death, and this resistance of the brain to injury is known as ischemic tolerance. Brief alternating periods of reperfusion-reocclusion at the beginning of reperfusion is defined as postconditioning. Cerebral ischemic pre/postconditioning protects against stroke, but is clinically feasible only when the occurrence of stroke is predictable. Brief, repetitive occlusion and release of the main trunk of a vessel during early aneurysm surgery or before long-lasting temporary artery occlusion may protect the brain against later possible vasospasm/ischemia.

Rod Migration to the Thoracic Subarachnoid Space after C1-2Instrumentation: A Case Report and Literature Review: Rod Migration after C1-2Instrumentation

Posterior instrumented fusion of the cervical spine is a common surgical procedure in the treatment of cervical subluxation, fractures, and stenosis. Although malpositions are commonly seen, it is rare to observe the malposition of the rod or interconnection because of hardware failure. A 62‐year‐old woman with spastic tetraparesis as a sequel to pediatric meningitis with C1–C2 cervical subluxation and myelomalacia had undergone laminectomy of C1 and C1 lateral mass and C2 bilateral pedicular screw fixation. Three years after the stabilization, she presented with complaints of headache, neck pain, and difficulty walking. There was no history of trauma during that period. A previously unrecorded and unusual migration of a rod through the thoracic subarachnoid space was detected. In this study, we report a case of atlantoaxial stabilization using the screw‐rod technique that was followed by rod migration to the thoracic subarachnoid space, and outline the subsequent management of the case. Failure of bony fusion can result in micromotion and subsequent migration of fixation device components. Routine radiographic follow‐up could be used to identify migration events.

Olea europaea Leaf Extract Improves the Efficacy of Temozolomide Therapy by Inducing MGMT Methylation and Reducing P53 Expression in Glioblastoma

ABSTRACT Unmethylated O6-methylguanine-DNA-methyltransferase (MGMT) promoter leads to Temozolomide (TMZ) resistance in most of the glioblastoma multiforme (GBM) patients. We previously investigated the synergistic effect of Olea europaea leaf extract (OLE) on TMZ cytotoxicity through modulating microRNA expression. To date, knowledge about the effect of OLE on MGMT methylation is insufficient. The aim of the current study was to evaluate the potential modulating effect of OLE on the TMZ response of GBM tumors through MGMT methylation. Exposure to 1 mg/mL OLE caused a significant induction of CpG island methylation in the MGMT gene using Methyl quantitative PCR assay (P < 0.001). In WST-1 analysis, the use of 350 µM TMZ plus 1 mg/mL OLE significantly increased the TMZ response of MGMT unmethylated cells (P = 0.003). Using the comet assay, the impact of 1 mg/mL OLE plus 350 µM TMZ on the formation of DNA strand breaks was significantly higher than that of 450 µM TMZ alone (P < 0.001) and Western blot analysis revealed that, when cells are treated with 1-mg/mL OLE, the total p53 protein levels tended to decrease. The results presented in this study uniquely demonstrated that OLE synergistically increased the TMZ response of GBM tumors by regulating MGMT gene methylation and p53 expression. However, further studies to validate our findings are required.

Olea europaea leaf extract and bevacizumab synergistically exhibit beneficial efficacy upon human glioblastoma cancer stem cells through reducing angiogenesis and invasion in vitro

Patients with glioblastoma multiforme (GBM) that are cancer stem-cell-positive (GSC [+]) essentially cannot benefit from anti-angiogenic or anti-invasive therapy. In the present study, the potential anti-angiogenic and anti-invasive effects of Olea europaea (olive) leaf extract (OLE) were tested using GSC (+) tumours. OLE (2mg/mL) caused a significant reduction in tumour weight, vascularisation, invasiveness and migration (p=0.0001, p<0.001, p=0.004; respectively) that was associated with reducing the expression of VEGFA, MMP-2 and MMP-9. This effect was synergistically increased in combination with bevacizumab. Therefore, our current findings may contribute to research on drugs that inhibit the invasiveness of GBM.

Effects of Systemic and Local Interferon Beta-1a on Epidural Fibrosis

Study Design Level 1 randomized controlled study. Purpose To investigate the effects of systemic and local interferon-beta-1a (IFN-β-1a) on prevention of epidural fibrosis using histopathological parameters. Overview of Literature Epidural fibrosis involves fibroblastic invasion of nerve roots into the epidural space. Formation of dense fibrous tissue causes lumbar and radicular pain. Many surgical techniques and several materials have been proposed in the literature, but no study has assessed the effect of IFN-β-1a on prevention of epidural fibrosis. Methods Forty-eight adult female Sprague-Dawley rats were divided into six groups of eight: sham group, control group, systemic 44 μg IFN-β-1a group and 22 μg IFN-β-1a group (after laminectomy and discectomy, 0.28 mL and 0.14 mL IFN-β-1a applied subcutaneously three times for a week, respectively), local 44 μg IFN-β-1a group (laminectomy and discectomy, followed by 0.28 mL IFN-β-1a on the surgical area), and local 22 μg IFN-β-1a group (laminectomy and discectomy, followed by 0.14 mL IFN-β-1a on the surgical area). All rats were sacrificed after 4 weeks and groups were evaluated histopathologically. Results Compared with sham and control groups, significantly less epidural fibrosis, dural adhesion, and fibroblast cell density were observed in the local and systemic 44 μg IFN-β-1a groups. No other differences were evident between the local and systemic groups. Conclusions IFN-β-1a is effective in preventing epidural fibrosis with systemic and local application.

Does glioblastoma cyst fluid promote sciatic nerve regeneration

Glioblastoma cyst fluid contains growth factors and extracellular matrix proteins which are known as neurotrophic and neurite-promoting agents. Therefore, we hypothesized that glioblastoma cyst fluid can promote the regeneration of injured peripheral nerves. To validate this hypothesis, we transected rat sciatic nerve, performed epineural anastomosis, and wrapped the injured sciatic nerve with glioblastoma cyst fluid- or saline-soaked gelatin sponges. Neurological function and histomorphological examinations showed that compared with the rats receiving local saline treatment, those receiving local glioblastoma cyst fluid treatment had better sciatic nerve function, fewer scars, greater axon area, counts and diameter as well as fiber diameter. These findings suggest that glioblastoma cyst fluid can promote the regeneration of injured sciatic nerve and has the potential for future clinical application in patients with peripheral nerve injury.