Glycogen synthase kinase-3 inhibition in glioblastoma multiforme cells induces apoptosis, cell cycle arrest and changing biomolecular structure

WOS: 000453111700019PubMed ID: 30388586Glioblastoma multiforme (GBM) is the most malignant and aggressive primary human brain tumors. The regulatory pathways of apoptosis are altered in GBMs, leading to a survival advantage of the tumor cells. Thus, identification of target molecules, which are effective in triggering of the cell death mechanisms in GBM, is an essential strategy for therapeutic purposes. Glycogen synthase kinase-3 (GSK-3) plays an important role in apoptosis, proliferation and cell cycle. This study focused on the effect of GSK-3 inhibitor IX in the GBM cells. Apoptosis induction was determined by Annexin-V assay, multicaspase activity and immunofluorescence analyses. Concentration-dependent effects of GSK-3 inhibitor IX on the cell cycle were also evaluated. Moreover, the effect of GSK inhibitor on the cellular biomolecules was assessed by using ATR-FTIR spectroscopy. Our assay results indicated that GSK-3 inhibitor IX induces apoptosis, resulting in a significant increase in the expression of caspase-3 and caspase-8 proteins. Cell cycle analyses revealed that GSK-3 inhibitor IX leads to dose -dependent G2/M-phase cell cycle arrest. Based on the FTIR data, treatment of GBM cells causes dysregulation in the carbohydrate metabolism and induces apoptotic cell death which was characterized by the spectral alterations in nucleic acids, an increment in the lipid amount with disordering state and compositional changes in the cellular proteins. These findings suggest that GSK-3 inhibitor IX exhibits anti-cancer effects by inducing apoptosis and changing biomolecular structure of membrane lipids, carbohydrates, nucleic acids and proteins, and thus, may be further evaluated as a potential effective candidate agent for the GBM combination therapies. (C) 2018 Elsevier B.V. All rights reserved

Ruptured distal anterior choroidal artery aneurysm

WOS: 000262348500031PubMed ID: 19013815This report describes a patient with a rare distal anterior choroidal artery (AChoA) aneurysm that developed a right intracerebral haematoma and intraventricular haemorrhage and was treated by surgical exploration and clipping via a transtemporal/ventricular approach. The patient was discharged neurologically intact. We review the literature related to these rare aneurysms within the temporal horn, and the surgical anatomy of the AChoA. Crown Copyright (C) 2008 Published by Elsevier Ltd. All rights reserved

A Rare History: an Intracranial Nail Present for Over a Half-Century

We present a rare case of a patient with a persistent headache for many years found to have an intracranial nail present for nearly 65 years. The nail was found entering approximately 1 cm from the midline on the left side, passing below the superior sagittal sinus, with the tip 1.5 mm right of the frontal horn of the lateral ventricle. Treatment strategies designed to optimize outcome for intracranial foreign bodies and possible complications are discussed in this report. We also discuss the decision for surgical intervention for foreign bodies and the relevance of position of the foreign body

The diagnostic value of complete blood count parameters in patients with subarachnoid hemorrhage

Objectives: Diagnosis of subarachnoid hemorrhage (SAH) in patients presenting with headache is challenging and there has been any biomarker studied for excluding of SAH in those patients. We aim to determine the sensitivity of leukocytosis or left shift to exclude the diagnosis of SAH in ED patients presenting with headache. Method: Adult patients with headache who received a computed tomography (CT) with the diagnosis of SAH and had a complete blood count (CBC) represent the case group, headache patients with normal CT and had a CBC represent the control group. The white blood cell (WBC) count and percentage of polymorphonuclear cells (PMNs%) taken during admission and within the first 6 and 12 h of admission were recorded. Results: A hundred ninety seven patients with SAH and 197 patients without SAH were enrolled in to study. Sensitivity, specificity, NPV and PPV of leukocytosis or increase in PMNs% (left shift) in the diagnosis of SAH was 89.8% (84.5â93.5, 95% CI), 46.7% (39.6â53.9, 95% CI), 82.1% (73.5â88.4, 95% CI) and 62.8% (56.8â68.4, 95% CI) respectively on initial emergency department (ED) admission. Conclusion: CBC should be considered as a noninvasive test for the exclusion of SAH in ED patients with 6 h observation. Keywords: Complete blood count, Subarachnoid hemorrhage, Emergency medicin

Effects of Lutein on Brain Damage and Vasospasm in an Experimental Subarachnoid Hemorrhage Model

© 2020 Elsevier Inc.Objective: Vasospasm developing after subarachnoid hemorrhage (SAH) is an important cause of mortality and morbidity. Lutein is a carotenoid with antioxidant and anti-inflammatory properties. The aim of present study was to investigate effects of lutein on the basilar artery and nerve tissues. Methods: Wistar rats were randomly divided into 3 groups: control (group 1), SAH (group 2), and SAH treated with lutein (group 3). Lutein was administered for 3 days by means of orogastric gavage. Basilar artery lumen area, wall thickness, serum total antioxidant status, serum total oxidant status, and oxidative stress index were calculated. Histopathologic and immunohistochemical analyses were conducted. Results: No statistically significant difference was found between groups in terms of wall thickness; lumen area; and serum total antioxidant status, serum total oxidant status, and oxidative stress index values. A statistically significant difference was found between groups colored with terminal deoxynucleotidyl transferase dUTP nick end labeling (P < 0.005). Post hoc analysis was used to examine the results between groups. Results of group 1 and group 3 were equal (P = 1) and lower than group 2 (P = 0.04 and P = 0.006, respectively). Conclusions: Lutein was found to have a positive effect on width of the basilar artery lumen area. Therefore, positive effects of lutein on vasospasm might be statistically significant if lutein is administered at higher doses. Lutein was found to be effective in preventing brain damage after SAH. To our knowledge, this study is the first in the literature to examine the effect of lutein on vasospasm and brain damage after SAH

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

###EgeUn###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.World Federat Neurosurg SocEge University scientific research project fundingEge University [16 TIP 039]This experimental study was supported by Ege University scientific research project funding (Project number: 16 TIP 039)

Does Decompressive Duraplasty Have a Neuroprotective Effect on Spinal Trauma?: An Experimental Study

WOS: 000469222400035PubMed ID: 30822587BACKGROUND: Spinal cord injury (SCI) may result in neuromotor, sensory, and autonomic function damages. Edema because of spinal cord trauma can reach serious dimensions. The aim of this study was to histologically evaluate the effects of duraplasty on neural tissues. METHODS: Twenty-eight Wistar rats were randomly divided into 4 experimental groups: group 1 received laminectomy without SCI (sham); group 2 received laminectomy and SCI with the weight drop method; group 3 received laminectomy, SCI, and duraplasty within the first 6-8 hours of SCI; and group 4 received laminectomy, SCI, and duraplasty after 24 hours of SCI. The neurologic functions of the rats were tested periodically. All animals were euthanized 28 days after the surgery. Histopathologic and immunohistochemical evaluations were performed, and Kruskal-Wallis tests were used for statistical comparison of data between the groups. RESULTS: There was no significant difference in the Tarlov examination scores from different time points between the groups. The number of neurons stained with nuclear factor kappa beta was higher in group 3 than groups 1 and 4. The number of neurons stained with terminal deoxynucleotidyl transferase dUTP nick-end labeling was higher in group 2 than group 3. CONCLUSIONS: Decompressive laminectomy is a procedure frequently used in spinal trauma surgery. However, it is often unclear whether the decompression is fully adequate. Our results will aid the development of further studies regarding the reliability of duraplasty in the treatment of SCI

Does Decompressive Duraplasty Have a Neuroprotective Effect on Spinal Trauma?: An Experimental Study

BACKGROUND: Spinal cord injury (SCI) may result in neuromotor, sensory, and autonomic function damages. Edema because of spinal cord trauma can reach serious dimensions. The aim of this study was to histologically evaluate the effects of duraplasty on neural tissues

Neurosurgical treatment of Cushing disease in pediatric patients: case series and review of literature

Aim Pituitary adenomas are rare in childhood in contrast with adults. Adrenocorticotropic hormone (ACTH)-secreting adenomas account for Cushing's disease (CD) which is the most common form of ACTH-dependent Cushing's syndrome (CS). Treatment strategies are generally based on data of adult CD patients, although some difficulties and differences exist in pediatric patients. The aim of this study is to share our experience of 10 children and adolescents with CD. Patients and method Medical records, images, and operative notes of 10 consecutive children and adolescents who underwent transsphenoidal surgery for CD between 1999 and 2014 in Cerrahpasa Faculty of Medicine were retrospectively reviewed. Mean age at operation was 14.8 +/- 4.2 years (range 5-18). The mean length of symptoms was 24.2 months. The mean follow-up period was 11 years (range 4 to 19 years). Results Mean preoperative cortisol level was 23.435 mu g/dl (range 8.81-59.8 mu g/dl). Mean preoperative ACTH level was 57.358 mu g/dl (range 28.9-139.9 mu g/dl). MR images localized microadenoma in three patients (30%), macroadenoma in four patients (40%) in our series. Transsphenoidal microsurgery and endoscopic transsphenoidal surgery were performed in 8 and 2 patients respectively. Remission was provided in 8 patients (80%). Five patients (50%) met remission criteria after initial operations. Three patients (30%) underwent additional operations to meet remission criteria. Conclusion Transsphenoidal surgery remains the mainstay therapy for CD in pediatric patients as well as adults. It is an effective treatment option with low rate of complications. Both endoscopic and microscopic approaches provide safe access to sella and satisfactory surgical results